by maha mahmoud ali mohammed · 2012. 8. 17. · maha mahmoud ali mohammed b.sc. zoology and...

The Possible Protective Role of Foeniculum vulgare Mill Against Radiation-Induced Certain

Biochemical Changes in Albino Rats

Thesis Submitted to Faculty of Science

Beni-Suif University In Partial Fulfillment of

Master Degree of Science

BY

Maha Mahmoud Ali Mohammed BSc Zoology and Chemistry

Under Supervision of Prof Dr Nour El-Din Amin Mohamed

Zoology Department Faculty of Science

Beni-Suef University 2010

Professor of Biological chemistry Drug Radiation Research Department

National Center for Radiation Research and Technology Atomic Energy Authority

DrOsama Mohamed Ahmed Assistant Professor of Physiology

Faculty of Science Beni-Suif University

DrEman Salah Abdel-Reheim Assistant professor of Physiology

Faculty of Science Beni-Suif University

Title of the M Sc Thesis

The Possible Protective Role of Foeniculum vulgare Mill Against Radiation Induced Certain Biochemical

Changes in Albino Rats

Name of Candidate


For Partial Fulfillment of the Master Degree of Science in Zoology

Submitted to Zoology Department Faculty of Science

Beni ndash Suef University

Supervision Committee

1 Prof Dr Nour El-Din Amin Mohamed

3 Dr Eman Salah Abdel-Reheim Assistant Professor of Physiology- Department of Zoology- Faculty of

Science- Beni-Suef University

Professor of Biological chemistry- Drug Radiation Research Department-

National Center for Radiation Research and Technology (NCRRT) - Atomic

Energy Authority

2 Dr Osama Mohamed Ahmed Assistant Professor of Physiology- Department of Zoology- Faculty of


Studied by the candidate

Beside the work presented in this thesis the candidate has

attended and passed successfully the following post-graduate courses

as a partial fulfillment of the degree of Master of Science during the

academic year 2005 2006-

-Haematology

-Water and Minerals Metabolism

-Histology and Histochemistry

-Cell Biology and Immunology

-Radiobiology

-Systemic Zoology

-Neurophysiology

-Endocrinology and Coordination

-Reproduction Physiology

-Sensory Physiology and Animal Behavior

-Biochemistry

-Toxicology

-Fresh water Ecology and Physiology

-Muscle Physiology

-Respiration and Excretion

-Biostatistics

Contents Page Acknowledgementhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip I List of abbreviations helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip Ii List of tables helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip Iii List of figureshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip Iv Abstracthelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip V 1 INTRODUCTIONhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 1-4

2 REVIEW OF LITERATURE 5

21 Radiation and its typeshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 211 Types of ionizing radiationhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 2111 Alpha particles helliphelliphelliphelliphelliphellip 2112 Beta particles helliphelliphelliphelliphelliphelliphellip 2113 Gamma ray helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 2114 X-ray helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 212 Types of non-ionizing radiationhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 213 Biological effects of ionizing radiationhelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 2131 Direct interactionhelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 2132 Indirect interactionhelliphelliphelliphelliphelliphelliphelliphelliphellip 214 Chemical consequences of ionizing radiationhelliphelliphelliphelliphelliphelliphelliphellip 215 Effects of ionizing radiation on liver functionshelliphelliphelliphelliphelliphelliphelliphelliphellip 216 Effects of ionizing radiation on protein profilehelliphelliphelliphelliphelliphelliphelliphelliphellip 217 Effects of ionizing radiation on renal functionshelliphelliphelliphelliphelliphelliphelliphelliphellip 218 Effects of ionizing radiation on lipid metabolismshelliphelliphelliphelliphelliphelliphelliphellip 219 Effects of ionizing radiation on serum testosteronehelliphelliphelliphelliphelliphelliphellip 2110 Effects of ionizing radiation on antioxidant defense statushelliphelliphelliphellip

5 5 6 6 6 7 7 8 8 9 10 11 12 13 14 16 17

2 2 Essential trace elementshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 221 Trace elements in radiation hazards (Radiation Protection and Recovery with essential metalloelements)helliphelliphelliphelliphelliphelliphelliphelliphellip 2211 Role of zinc in radiation protection and recoveryhelliphelliphelliphelliphelliphelliphellip - Effect of gamma-irradiation on Zn metabolismhelliphelliphelliphelliphelliphelliphelliphellip 2212 Role of copper in radiation protection and recoveryhelliphelliphelliphelliphelliphellip - Effect of gamma-irradiation on Cu metabolismhelliphelliphelliphelliphelliphelliphelliphellip 2213 Role of iron in radiation protection and recoveryhelliphelliphelliphelliphelliphelliphellip - Effect of gamma-irradiation on Fe metabolismhelliphelliphelliphelliphelliphelliphelliphellip 2214 Role of selenium in radiation protection and recoveryhelliphelliphelliphelliphellip - Effect of gamma-irradiation on Se metabolismhelliphelliphelliphelliphelliphelliphelliphellip 2215 Role of calcium in radiation protection and recoveryhelliphelliphelliphellip - Effect of gamma-irradiation on Ca metabolismhelliphelliphelliphelliphelliphelliphelliphellip 2216 Role of magnesium in radiation protection and recoveryhelliphelliphelliphelliphellip - Effect of gamma-irradiation on Mg metabolismhelliphelliphelliphelliphelliphellip 2217 Role of manganese in radiation protection and recoveryhelliphelliphelliphelliphellip - Effect of gamma-irradiation on Mn metabolismhelliphelliphelliphelliphelliphelliphelliphellip

22 24

25 27 27 28 29 30 31 33 33 34 35 35 36 37

23 Role of Medicine plants in Radiation Recoverieshelliphelliphellip 231 Chemical constituents of Foeniculum vulgare Millhelliphelliphelliphelliphellip

232 Absorption metabolism and excretionhelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 233 Mechanism of actionhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 234 Biological efficacy of Foeniculumm vulgare Millhelliphelliphelliphelliphelliphellip

38 40 41 42 43

3 AIM and Objectiveshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

47

4 MATERIALS amp METHODShelliphelliphelliphelliphelliphelliphelliphelliphellip

48

41 Materialshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 411 Experimental Animalshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 412 Radiation processinghelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 413 Treatmenthelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 414 Samplinghelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4141 Blood sampleshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4142 Tissue samplinghelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 415 Chemicalshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 416 Apparatushelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 417 Experimental design (animal grouping)helliphelliphelliphelliphelliphelliphelliphellip 4 2 Methodshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 421 Assay of various biochemical parameters in serumhelliphellip 4211 Determination of ALT activityhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4212 Determination of AST activityhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4213 Determination of ALP activityhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4-214 Determination of bilirubin activityhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4215 Determination of total protein concentrationhelliphelliphelliphelliphelliphelliphellip 4216 Determination of albumin concentrationhelliphelliphelliphelliphelliphelliphelliphelliphellip 4217 Determination of serum globulin concentration and albumin globulin (AG) ratiohelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4218 Determination of urea concentrationhelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4219 Determination of creatinine concentrationhelliphelliphelliphelliphelliphelliphelliphellip 42110 Determination of cholesterol concentrationhelliphelliphelliphelliphelliphelliphelliphellip 42111 Determination of triglyceride concentration helliphelliphelliphelliphelliphelliphellip 42112 Determination of serum testosterone concentration helliphelliphelliphellip 422 Assay of different variables in tissue homogenatehelliphelliphellip 4221 Measurement of lipid peroxidation (LPO)helliphelliphelliphelliphelliphelliphelliphellip 4222 Measurement of metallothioneins (MTs)helliphelliphelliphelliphelliphelliphelliphelliphellip 4223 Determination of glutathione reduced (GSH)helliphelliphelliphelliphelliphelliphellip 423 ATOMIC ABSORPTION PHOTOMETERYhelliphelliphelliphellip 4231 Theoryhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4232 Interferencehelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4233 Instrumentationhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 4234 Sample preparationhelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 42341 Tissue sampleshelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip 42342 Microwave Digestor Technologyhelliphelliphelliphelliphelliphelliphelliphellip 424 Statistical analysishelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

48 48 48 48 48 48 49 49 50 50

51 51 51 51 52 52 53 53 53

54 54 54 55 55 56 56 56 58 58 58 59 59 61 61 61 62

5 RESULTS helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

63

6 DISCUSSION helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

94

7 SUMMARY amp CONCLUSION helliphelliphelliphelliphelliphelliphellip

124

8 REFERENCES helliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphelliphellip

126

Arabic summary

Acknowledgement

I

(First of All Thanks to GOD)

I can but inadequately express my gratitude and sincere thanks to

Professor Dr Nour El-Din Amin Mohamed Professor of Biological chemistry

Drug Radiation Research Department National Center for Radiation Research

and Technology (NCRRT) Atomic Energy Authority (AEA) for suggesting the

line of research investigated keen supervision valuable guidance and

encouragement He offered deep experience and continuous support

The candidate expresses his deepest gratitude and sincere appreciation to

Dr Osama Mohamed Ahmed Mohamed Assistant Professor of physiology

Zoology Department Faculty of Science Beni-Suef University for his kindness

valuable advices and for his support throughout this work and supervising this

work being

I would like to express my sincere thanks and appreciation to Dr Eman

Salah Abdel-Reheim Assistant Professor of Physiology Zoology Department

Faculty of Science Beni-Suef University for her kindness valuable advices and

for supervising this work being and encouraging me to the better

Also I would like to express my deep gratitude to Dr Ahmed Shafik

Nada Assistant Professor of physiology Drug Radiation Research Department

National Center for Radiation Research and Technology (NCRRT) Atomic

Energy Authority (AEA) for his kindness valuable advices and helping in every

step of this work and encouraging me to the better He offered all things effort

and deep experiences to stimulate me and push me forward

Acknowledgement

I

A special word of gratefulness is directed to the head and all members of

the department of Drug Radiation Research for their constant help and

encouragement

I would like to give my appreciation to the head and all my colleagues at

various scientific and technical divisions of National Center for Radiation

Research and Technology (NCRRT) with special reference to the staff member of

gamma irradiation unit for their unforgettable cooperation in carrying out

experimental irradiation

Finally thanks are expressed to the members of Zoology Department

Faculty of Science Beni-Suef University

I must offer my truly deepest appreciation and heartily thanks for my

father mother brothers sisters and my friends for their great help and support

`tt `tAringEacuteacircw TAuml|

List of Abbreviations

Ii

Alkaline phosphatase ALP Alanine transaminases ALT Analysis of variance ANOVA Antioxidant defense system AODS Aspartate transaminases AST Body weight bwt Catalase CAT Cholesterol Ch Ceruplasmin Cp Cytochrome P450 CYP Diethyl dithiocarbamate DDC Diribonucleic acid DNA 22-diphenyl-1-picryl hydrazyl DPPH Double strand breaks DSB 5 5 dithiobis (2- nitrobenzoic acid) DTNB Foeniculum vulgare essential oil FEO Fennel seed FS Foeniculum vulgare FV Glucose 6- phosphate dehydrogenase G-6-PD Glumerular filtration rate GFR Gamma glutamyl-transferase GGT Gluathione peroxide GPX Reduced glutathione GSH Glutathione peroxidase GSHpx Oxidized glutathione GSSG Glutathione S- transferase GST Gray Gy Hydrogen peroxide H2O2 High density lipoprotein cholesterol HDL-C 3- Hydroxyl - 3- methyl glutaryl coenzyme A HMG-COA Interperitonial IP Lactate dehydrogenase LDH Lactate dehydrogenase enzyme LDH-X


Ii

Low density lipoprotein cholesterol LDL-C Lipid peroxidation LPO Mitogen activated protein kinase MAPK Malondialdehyde MDA Manganese superoxide dismutase Mn-SOD Messenger ribonucleic acid mRNA Metallothionieins MTs Nicotinamide adenine dinucleotide phosphate hydrogen NADPH Naiumlve lymphocyte NL Nitric oxide NO Nitric oxide radical NOmiddot Nitric oxide synthase NOS Superoxide radical O2

- Hydroxyl radical OH Peroxynitrite ONOO- Protein Kinase C PKC Reactive oxygen species ROS Superoxide dismutase SOD Thiobarbituric acid TBA Thiobarbituric acid reactive substance TBARS Trichloroacetic acid TCA Total cholesterol TC Triglyceride TG Tumor necrosis factor TNF

List of Tables

Iii

Table

Page

1 Effect of Foeniculum vulgare essential oil (FEO) on serum AST ALT and ALP activities in normal irradiated and treated rats

64

2 Effect of Foeniculum vulgare essential oil (FEO) on serum bilirubin activity in normal irradiated and treated rats

66

3 Effect of Foeniculum vulgare essential oil (FEO) on protein profile activities in normal irradiated and treated rats

68

4 Effect of Foeniculum vulgare essential oil (FEO) on serum urea and creatinine concentrations in normal irradiated and treated rats

70

5 Effect of Foeniculum vulgare essential oil (FEO) on serum cholesterol and triglyceride concentrations in normal irradiated and treated rats

72

6 Effect of Foeniculum vulgare essential oil (FEO) on serum testosterone concentration in normal irradiated and treated rats

74

7 Effect of Foeniculum vulgare essential oil (FEO) on antioxidant status in liver fresh tissues of normal and irradiated rats

76

8 Effect of Foeniculum vulgare essential oil (FEO) on antioxidant status in kidney fresh tissues of normal and irradiated rats

78

9 Concentration levels of Zn (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

80

10 Concentration levels of Cu (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

82

11 Concentration levels of Fe (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

84

12 Concentration levels of Se (ngg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

86

List of Tables

Iii

13 Concentration levels of Ca (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

88

14 Concentration levels of Mg (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

90

15 Concentration levels of Mn (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

92

16 Concentration levels of metal in fennel plant (microgg) for all metal except Se (ngg)

93

List of figures

Iv

Figure Foeniculum vulgare Mill (Franz et al 2005) 39

2 Chemical Structure of fennel trans-anethole (a) estragole (b) and fenchone(c) (Bilia et al 2000 Fang et al 2006)

40

3 The putative mechanisms of radioprotection by various plants and herbs (Jageta 2007)

42

4 Effect of FEO on liver functions of normal and irradiated rats

64

5 Effect of FEO on serum bilirubin of normal and irradiated rats

66

6 Effect of FEO on serum protein profile of normal and irradiated rats

68

7 Effect of FEO on serum urea and creatinine concentrations of normal and irradiated rats

70

8 Effect of FEO on cholesterol and triglyceride of normal and irradiated rats

72

9 Effect of FEO on serum testosterone concentration of normal and irradiated rats

74

10 Effect of FEO on antioxidant status in liver fresh tissues of normal and irradiated rats

76

11 Effect of FEO on antioxidant status in kidney fresh tissues of normal and irradiated rats

78

12 Concentration levels of Zn in different tissue organs of different rat groups

80

13 Concentration levels of Cu in different tissue organs of different rat groups

82

14 Concentration levels of Fe in different tissue organs of different rat groups

84

15 Concentration levels of Se in different tissue organs of different rat groups

86

16 Concentration levels of Ca in different tissue organs of different rat groups

88

17 Concentration levels of Mg in different tissue organs of different rat groups

90

18 Concentration levels of Mn in different tissue organs of different rat groups

92

Abstract

V

This study was conducted to evaluate the modulating efficacy of

prolonged oral administration of Foeniculum vulgare Mill essential oil (FEO) against gamma irradiation-induced biochemical changes in male rats Essential oil of Foeniculum vulgare Mill was orally administrated at dose level of 250 mgkg body wtday for 21 days before irradiation and 7 days post exposure (65 Gy single dose) Rats exposed to ionizing radiation exhibited a potential elevation of serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities bilirubin urea and creatinine levels lipid abnormalities and an increase in tissue lipid peroxidation (LPO) and metallothioneins (MTs) On the other hand noticeable drop in liver and kidney glutathione content and serum total protein albumin and testosterone levels were recorded Tissue organs displayed some changes in trace element concentrations which may be due to the radiation ability to induce oxidative stress The data obtained from rats treated with fennel oil before and after whole body gamma irradiation revealed significant modulation in the biochemical tested parameters and profound improvement in the activity of antioxidant status glutathione and metallothioneins The treatment of irradiated rats with fennel oil also appeared to be effective in minimizing the radiation-induced increase in lipid peroxidation as well as changes in essential trace elements in some tissue organs In addition to its containing many chemical antioxidant constituents such as polyphenols fennel was found to contain detectable concentrations of essential trace elements (Zn Cu Fe Se Mg Mn and Ca) which may be involved in multiple biological processes as constituents of enzymes system including superoxide dismutase (Cu Zn Mn SODs) oxide reductase glutathione (GSP GSH GST) metallothionein MTs etc Overall it could be concluded that Foeniculum vulgare Mill essential oil exerts beneficial protective role against radiation-induced deleterious biochemical effects related to many organ functions and deteriorated antioxidant defense system

Introduction

١

Exposure to ionizing radiation causes many health hazardous effects

Such exposure produces biochemical lesions that initiate a series of

physiological symptoms Reactive oxygen species (ROS) such as

superoxide (O2-) hydroxyl radical (OH) and hydrogen peroxide (H2O2)

created in the aqueous medium of living cells during irradiation cause lipid

peroxidation in cell membrane and damage to cellular activities leading to a

number of physiological disorders situation and dysfunction of cells and

tissues (Cho et al 2003 Spitz et al 2004) ROS are the cause of certain

disease such as cancer tumors cardiovascular diseases and liver

dysfunction (Florence 1995) Ionizing radiation passing through living

tissues generates free radical that can induce DNA damage The damaging

effects of ionizing radiation on DNA lead to cell death and are associated

with an increased risk of cancer (Halliwell and Aruoma 1991 Azab and

El-Dawi 2005)

To maintain the redox balance and to protect organs from these free

radicals action the living cells have evolved an endogenous antioxidant

defense mechanism which includes enzymes like catalase (CAT)

superoxide dismutase (SOD) glutathione peroxidase (GSHpx) in addition

to reduced glutathione (GSH) and metallothioniens (MTs) Radiation

exposure alters the balance of endogenous defense systems Appropriate

antioxidant intervention seems to inhibit or reduce free radicals toxicity and

offer a protection against the radiation damage A number of dietary

antioxidant has been reported to decrease free radical attack on

biomolecules (Halliwell and Gutteridge 2004)

Introduction

٢

There is at present growing interest both in the industry and in the

scientific research for aromatic and medicinal plants because of their

antimicrobial and antioxidant properties These properties are due to many

active phytochemicals including flavanoids terpenoids carotenoids

coumarins curcumines etc these bioactive principles have also been

confirmed using modern analytical techniques (Soler-Rivas et al 2000

Koleva et al 2001) Hence they are considered to be important in diets or

medical therapies for biological tissue deterioration due to free radicals

Herbs and spices are amongst the most important targets to search for

natural antimicrobials and antioxidants from the point of view of safety (Ito

et al 1985)

Many natural and synthetic compounds have been investigated for

their efficacy to protect against irradiation damage (Nair et al 2004)

Previous studies developed radioprotectve and radiorecovery agents to

protect from the indirect effects of radiation by eliminating free radical

produced in response to radiation (Tawfik et al 2006a) Supplementary

phytochemicals including polyphenols flavonoids sulfhydryl compounds

plant extracts and immunomodulators are antioxidants and radioprotective

in experimental systems (Tawfik et al 2006b) Scientific studies available

on a good member of medicinal plants indicate that promising

phytochemicals can be developing for many health problems (Gupta

1994)

Spices the natural food additives contribute immensely to the taste

and flavour of our foods These esoteric food adjuncts have been in use for

thousands of years Spices have also been recognized to posses several

medicinal properties and have been effectively used in the indigenous

system of medicine (Srinivasan 2005) Traditionally fennel has been

Introduction

٣

consumed as a spice However there is more interest in other potential

uses particularly as an essential oil which has proven as a good

hepatoprotective effects (Oumlzbec et al 2004) antimicrobial (Soylu et al

2006) and antioxidant (El-SN and KaraKaya 2004) It has recently

become clear that one of the values of many spices is that they contain

natural antioxidants which provide protection against harmful free

radicals

Fennel (Foeniculum vulgare Mill family umbelliferae) is an annual

biennial or perennial aromatic herb depending on the variety which has

been known since antiquity in Europe and Asia Minor The leaves stalks

and seeds (fruits) of the plant are edible Trans-anethole (50-80) and

fenchone (5) are the most important volatile components of Foeniculum

vulgare volatile oil and are responsible for its antioxidant activity In

addition other constituents such as estragole (methyl chavicol) safrol D-

limonene 5 α-pinene 05 camphene β-pinene β-myrcene α-

phellandren P-cymene 3-carnene camphor and cis-anethole were found

(Simandi et al 1999 Ozcan et al 2001) Both extracts and essential oil

of fennel is known to posses hepatoprotective effects (Oumlzbec et al 2004)

antioxidant activities (EL-SN and KaraKaya 2004) estrogenic activities

(Albert-Puleo 1980) antitumor activities in human prostate cancer (Ng

and Figg 2003) acaricidal activities (Lee 2004) antifungal effects

(Mimica-Dukic et al 2003) in addition to antimicrobial prosperities

(Soylu et al 2006) Also fennel (anethol) used in cancer prevention

(Aggarwal et al 2008) as well as immunomodulatory activities by

enhancing natural killer cell functions the effectors of the innate immune

response (Ibrahim 2007ab)

Introduction

٤

Copper Iron zinc and selenium are essential metalloelements

These essential metalloelements as well as essential amino acids essential

fatty acids and essential cofactors (vitamins) are required by all cells for

normal metabolic processes but cant be synthesized de novo and dietary

intake and absorption are required to obtain them (Lyengar et al 1978)

Copper iron manganese and zinc dependent enzymes have roles in

protecting against accumulation of ROS as well as facilitating tissue repair

(Sorenson 1978) These essential trace elements are involved in multiple

biological processes as constituents of enzyme system including superoxide

dismutase (Cu Zn Mn SODs) oxide reductase glutathione (GSHpx

GSH GST) metallothioneins (MTs) etc (Sorenson 2002) These metals

increased the antioxidant capacities the induction of metalloelements

dependent enzymes these enzymes play an important role in preventing the

accumulation of pathological concentration of oxygen radicals or in

repairing damage caused by irradiation injury (Sorenson 1992) The

highly content of essential trace elements in Foeniculum vulgare Mill may

offer a medicinal chemistry approach to overcoming radiation injury

(Sorenson 2002)

Review of literature

٥

21 Radiation and its types Radiation is the emission or transfere of radiant energy in the form of

waves or particles Radiation is a form of energy There are two basic types

of radiation ionizing and non-ionizing radiation The difference between

these two types is the amounts of energy they have Ionizing radiation is a

radiation emitted by radionuclides which are elements in an unstable form

It can cause structural changes by removing electrons from atoms and

leaving behind a charged atom (ion) Ionizing radiation is high-energy

radiation that has the ability to break chemical bonds cause ionization and

produce free radicals that can result in biological damage Non-ionizing

radiation doesnt result in structural changes of atoms (it doesnt cause

ionization) Non-ionizing radiation includes radiation from light radio

waves and microwaves Non-ionizing radiation does not have enough

energy to cause ionization but disperses energy through heat and increased

molecular movement (Prasad 1984 Hall 2000) 211 Types of ionizing radiation Ionizing radiation consisted of both particles and electromagnetic

radiation The particles are further classified as electrons protons neutrons

beta and alpha particles depending on their atomic characteristics The most

common electromagnetic radiation with enough energy to produce ions

break chemical bonds and alter biological function is x-rays and gamma

rays Exposure to such radiation can cause cellular changes such as

mutations chromosome aberration and cellular damage (Morgan 2003)


٦

2111 Alpha particle

An alpha particle consists of two neutrons and two protons ejected

from the nucleus of an atom The alpha particle is identical to the nucleus

of a helium atom Alpha particles are easily shielded against it and can be

stopped by a single sheet of paper Since alpha particles cant penetrate the

dead layer of the skin they dont present a hazard from exposure external to

the body However due to the very large number of ionizations they

produce in a very short distance alpha emitters can present a serious

hazard when they are proximity to cells and tissues such as the lung

Special precautions are taken to ensure that alpha emitters are not inhaled

injected or ingested (NRC 1990)

2112 Beta particles

A beta particle is an electron emitted from the nucleus of a

radioactive atom Examples of beta emitters commonly used in biological

research are hydrogen-3 (tritium) Beta particles are much less massive

and less charged than alpha particles and interact less intensely with atoms

in the materials they pass through which gives them a longer range than

alpha particles All beta emitters depending on the amount present can

pose a hazard if inhaled ingested or absorbed into the body In addition

energetic beta emitters are capable of presenting an external radiation

hazard especially to the skin Beta particles travel appreciable distances in

air but can be reduced or stopped by a layer of clothing thin sheet of

plastic or a thin sheet of aluminum foil (Cember 1996)

2113 Gamma ray A gamma ray is a packet or (photons) of electromagnetic radiation

emitted from the nucleus during radioactive decay and occasionally

accompanying the emission of an alpha or beta particle Gamma rays are


٧

identical in nature to other electromagnetic radiations such as light or

microwaves but are of much higher energy Examples of gamma emitters

are Cobalt-60 Zinc-65 Cisium-137 and Radium-226

Like all forms of electromagnetic radiation gamma rays have no

mass or charge and interact less intensively with matter than ionizing

particles Because gamma radiation losses energy slowly gamma rays are

able to travel significant distances Depending upon their initial energy

gamma rays can far travel tens or hundreds of feet in air Gamma radiation

is typically shielded using very dense materials (the denser the material the

more chance that gamma ray will interact with atoms in the material)

Several feet of concrete or a thin sheet of a few inches of lead may be

required to stop the more energetic gamma rays (Turner 1995)

2114 X-ray radiation Like gamma ray an x-ray is a packet or (photons) electromagnetic

radiation emitted from an atom except that the x-ray is not emitted from

the nucleus X-ray is produced as the result of changes in the positions of

the electrons orbiting the nucleus as the electrons shift to different energy

levels Examples of x-ray emitting radio-isotopes are iodine-125 and

iodine-131 A thin layer of lead can stop medicinal X-rays (William

1994)

212 Types of non-ionizing radiation Non- ionizing radiations are not energetic enough to ionize atoms

and interact with materials in ways that create different hazards than

ionizing radiation Examples of non-ionizing radiation include

microwaves visible light radio waves TV waves and ultra violet waves

light (Ng 2003)


٨

213 Biological effects of ionizing radiation When the living organisms are exposed to ionizing radiation they

could be affected either directly or indirectly or by both effects The effects

of irradiation on biological matter have been studied extensively

According to Mettler and Mosely (1987) when a cell or tissue is

exposed to radiation several changes occur eg

1 Damage to the cell membrane through lipid peroxidation

2 Damage to either one or both strands of deoxyribonucleic acid (DNA)

3 Formation of free radicals causing secondary damage to cells

Considering the above radiation can lead to damage in two ways

2131 Direct interaction In direct interaction a cells macromolecules (proteins or DNA) are

hit by ionizing radiation which affects the cell as a whole either killing the

cell or mutating the DNA (Nais 1998) A major mechanism of effect is the

ionizing damage directly inflicted up on the cells DNA by radiation

(Ward 1988 Nelson 2003)

Mettler and Moseley (1987) suggest that if only one strand of DNA

is broken by ionizing radiation repair could occur within minutes

However when both strands of DNA are broken at about the same

position correction would be much less likely to occur but if there are a

large number of ionizations in a small area (more than one single break in

the DNA strand) the local cell repair mechanisms become overwhelmed

In such cases the breaks in DNA may go unrepaired leading to cell

mutations (Altman and Lett 1990) Unrepaired DNA damage is known to

lead to genetic mutations apoptosis cellular senescence carcinogenesis

and death (Wu et al 1999 Rosen et al 2000 Oh et al 2001)


٩

2132 Indirect interaction Ionizing radiation affects indirectly via the formation of free radicals

(highly reactive atoms or molecules with a single unpaired electron) These

radicals may either inactivate cellular mechanisms or interact with the

genetic material (DNA) The ionizing effects of radiation also generate

oxidative reactions that cause physical changes in proteins lipids and

carbohydrates impairing their structure andor function (Lehnert and

Iyer 2002 Spitz et al 2004) Indirect interaction occurs when radiation

energy is deposited in the cell and the radiation interacts with cellular water

rather than with macromolecules within the cell The reaction that occurs is

hydrolysis of water molecules resulting in a hydrogen molecule and

hydroxyl free radical molecule (Dowd and Tilson 1999)

H2O (molecule) + ionizing radiation H+ + OH־

= (hydroxyl free radical) Recombination of

H+ + H+ H2 = hydrogen gas

H+ + OH־ H2O = water

Antioxidants can recombine with the OH- free radical and block

hydrogen peroxide formation If not then the 2 hydrogen ions could do the

following

OH־ + OH־ H2O2 = hydrogen peroxide formation

H2O2 H+ + HO2 unstable peroxide = ־

HO2 organic molecule Stable organic peroxide + ־

Stable organic peroxide Lack of essential enzyme

Eventual cell death is possible (Dowd and Tilson 1999)


١٠

214 Chemical consequences of ionizing radiation Since water represents 70 of the chemical composition of the adult

body (90 of the infant body) its chemical transformation by ionizing

radiation merits serious consideration with regard to chemical

consequences of ionizing radiation Ionizing radiolysis of water is well

understood and produces very reactive aquated electrons monoatomic

hydrogen atoms hydroxyl radical hydrogen peroxide and protonated

water as well as superoxide (O2-) and hydroperoxyl radical in the presence

of oxygen Hydroperoxyl radical hydroxyl radical monoatomic hydrogen

and aquated electrons have very short half lifes of the order of

milliseconds and consequently react rapidly with cellular components in

reduction oxidation initiation insertion propagation and addition

reactions causing loss of function and the need for biochemical

replacement andor repair (Halliwell and Gutteridge 2004) Ionizing

radiation can also impart sufficient energy to all biochemicals to cause

hemolytic bond breaking and produce all conceivable organic radicals in

considering C-C C-N C-O C-H P-O S-O etc bond homolysis These

radical will undergo the above listed radical reactions to cause further

destruction and the need for replacement andor repair (Droumlge 2002) A

third consequence of ionizing radiation is hemolytic or heterolytic bond

breaking of coordinate covalent bonded metalloelements These are the

weakest bonds in biochemical molecules and potential sites of greatest

damage which may be the most in need of replacement and or repair since

many repair enzymes are metalloelements dependent as are the

metalloelement dependent protective superoxide dismutase SODs (Hink et

al 2002)


١١

215 Effects of ionizing radiation on liver function

Several investigators postulated that the effect of irradiation on the

activity of aspartate aminotransferase (AST) and alanine aminotransferase

(ALT) reflects the degree of liver injury (Sallie et al 1991 Ramadan et

al 2002) In addition changes in the same serum enzymes (AST and

ALT) are considered useful indicators in detecting sub-clinical

hepatocellular damage (Sridharan and Shyamaladevi 2002) In view of

the effect of X-irradiation on transaminases El-Naggar et al (1980)

observed mild increase in the levels of both enzymes on the 7th day post

irradiation

Many investigators indicated that whole body gamma irradiation

caused elevation in transaminases (AST and ALT) as well as alkaline

phosphatase (ALP) (Ramadan et al 2001 Ramadan et al 2002 Abou-

Seif et al 2003a Mansour 2006 Kafafy et al 2006 Nada 2008)

Abdel-Hamid (2003) indicated that the decrease obtained in the

haematological picture due to the destruction of cells induced by irradiation

promoted the liberation of transaminases with high levels in blood

Acute whole body irradiation with different dose levels of gamma

rays (025 to 8 Gy) induces significant increase in the activities of AST and

ALT in 1 2 3 and 4 weeks post irradiation (Azab et al 2001) Similar

biochemical changes were observed by Abou-Seif et al (2003a) after

fractionated whole body irradiation by gamma rays and by Korovin et al

(2005) after fractionated whole body irradiation by X-rays

Sallam (2004) reported that the significant increase in mice serum

transaminases induced by gamma-irradiation (4 Gy) is caused either by


١٢

interaction of cellular membranes with gamma rays directly or indirectly

through an action of free radicals produced by this radiation

Kafafy et al (2005a) observed significant increase in serum ALT

activity accompanied with significant decrease in serum AST in pregnant

rats that received (3 Gy) gamma-irradiation El-Missiry et al (2007)

reported that the levels of AST ALP and gamma glutamyltransferase

(GGT) were significantly increased in sera of irradiated rats with dose of 2

and 4 Gy

Pradeep et al (2008) reported that rats which exposed to gamma

irradiation (1Gy 3Gy 5 Gy) resulted in an increase in AST ALT ALP and

GGT Also Adaramoye et al (2008) observed that exposure of male

wistar albino rats to gamma radiation (4 Gy)-induced liver damage

manifested as an increase in serum ALT AST activity and bilirubin content

at 24 hours after irradiation

Gamma-irradiation (5Gy) induced a significant elevation in the level

of rat serum bilirubin after a period of 60 days (Ashry et al 2008)

Mansour and El-Kabany (2009) indicated that exposure of rats to

gamma-irradiation (2Gy- 8Gy) resulted in an increase in AST ALT ALP

GGT activities and bilirubin (total and direct) content Similar biochemical

changes were observed by Omran et al (2009) who stated that 15 Gy

gamma-irradiated groups for 5 days receiving final dose up to 75 Gy

resulted in an increase in AST ALT ALP and bilirubin compared to

control one

216 Effect of ionizing radiation on protein profile

Badr El-din (2004) stated that a single dose of total body gamma

irradiation (65 Gy) to mice induced detectable decrease in total protein


١٣

El-Missiry et al (2007) reported that the levels of albumin total

protein and total globulin were significantly decreased in sera of irradiated

rats with dose of 2 and 4 Gy Also Ali et al (2007) revealed that total

protein in rats exposed to whole body gamma irradiation declined

compared to control group

Exposures of rats to gamma-ray and CCL4 separately or in

combination resulted in a marked decrease in serum total protein compared

to control (Ashry 2008) El-Tahawy et al (2009) reported that gamma-

irradiation 6 Gy caused a significant decrease in albumin level compared to

control

217 Effect of ionizing radiation on renal functions Many authors reported that ionizing radiation greatly affected renal

function (Ramadan et al 1998 Kafafy et al 2005a) They explained

that irradiation leads to biochemical changes in the irradiated animals

which may suffer from continuous loss in body weight which could be

attributed to disturbances in nitrogen metabolism usually recognized as

negative nitrogen balance Accordingly it could be expected that this may

cause an increase in the urea level ammonia concentration and amino acid

contents in blood and urine due to great protein destruction induced by

gamma irradiation Also increases of creatinine have been reported after

exposure to irradiation it is an evidence of marked impairment of kidney

function (Best and Taylor 1961)

Ramadan et al (2001) stated that a single dose of irradiation (6 Gy)

caused renal damage manifested biochemically as an increase in blood

urea Also Abou-Seif et al (2003a) reported that exposure of female

albino rats to whole body gamma irradiation at a dose level of 6 Gy caused


١٤

the mean activity values of blood urea creatinine and total cholesterol to

be significantly elevated

Moreover Badr El-din (2004) stated that a single dose of total body

gamma irradiation 65 Gy to mice induced significant elevation in plasma

creatinine urea and in urine protein concentration and also detectable

decrease in plasma total protein and urine creatinine levels Kafafy et al

(2005a) revealed that irradiation of rats caused significant drop in serum

total protein elevation in serum uric acid urea and creatinine

Also Kafafy et al (2006) found that irradiation significantly

elevated serum urea uric acid and creatinine while it declined total proteins

and albumin Creatinine was significantly increased in sera of irradiated

rats with dose of 2 and 4 Gy

218 Effects of ionizing radiation on lipid metabolisms Lipid profile especially cholesterol has being representing a major

essential constituent for all animal cell membranes (Gurr and Harwood

1992) Plasma lipid levels are affected by genetic and dietary factors

medication and certain primary disease states (Feldman and KusKe

1989) hyperlipidemia occurring due to exposure to ionizing radiation

resulting in accumulation of cholesterol triglycerides and phospholipids

(Stepanov 1989) The accumulated lipoproteins were susceptible to

peroxidation process causing a shift and imbalance in oxidation stress

(Dasgupta et al 1997) This imbalance manifested themselves through

exaggerated reactive oxygen species (ROS) production and cellular

molecular damage (Romero et al 1998)

Abou-Seif et al (2003a) observed significant elevation in

cholesterol level 24 hrs after whole body gamma irradiation (6 Gy) Again


١٥

an increase in serum cholesterol and triglyceride levels was observed in

female rats exposed to sub-lethal fractionated dose (Kafafy et al 2005b)

Zahran et al (2003) reported that rats exposed to ionizing radiation

showed significant alteration in plasma triglycerides and phospholipids

total cholesterol and low density lipoproteins (LDL)-cholesterol

concentrations indicating lipid metabolism disturbances Noaman et al

(2005) reported that exposure to ionizing radiation resulted in significant

alterations in free fatty acids neutral lipids and phospholipids of plasma

and liver after 24 and 48 hrs of gamma-irradiation indicating lipid

metabolism disturbances Plasma cholesterol and phospholipids levels

increased after 24 hrs from gamma radiation exposure

Also Mansour (2006) showed that gamma irradiation induced a

significant increase in Ch TG HDL and LDL levels after exposure to 6 Gy

irradiation compared to control group This confirms previous reports that

whole body exposure to gamma irradiation induces hyperlipidemia

(Feurgard et al 1998 El-Kafif et al 2003)

The levels of total lipids cholesterol triglyceride low density

lipoprotein were significantly increased in serum of the irradiated rats with

a dose of 2 and 4 Gy (El-Missiry et al 2007) While Ali et al (2007)

found that blood cholesterol and triglycerides in rats exposed to γ-

irradiation (65 Gy) were significantly increased

Tawfik and Salama (2008) showed that whole body gamma

irradiation of mice produced biochemical alteration in lipid profile fractions

triglyceride (TG) total cholesterol (TC) low density lipoprotein

cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C)

Similar biochemical alterations were observed by Nada (2008) after whole


١٦

body gamma irradiation (65 Gy) manifested by elevation in Ch TG and

LDL-C

219 Effect of ionizing radiation on serum testosterone

Radiation can change the characteristics of the cell nucleus and

cytoplasm as mammalian germ cells are very sensitive to ionizing

radiation (Dobson and Felton 1983) Ionized radiation being one of the

environmental cytotoxic factors causes death of the germinal cells and

therefore sterility (Meistrich 1993 Georgieva et al 2005)

In experimental studies radiation has been shown to induce both

acute and chronic damage to leydig cells of prepubertal and adult rats as

decreased testosterone secretion and increased gonadotropin release are

reported (Delic et al 1985 1986ab)

Pinon-Lataillade et al (1991) reported that acute exposure of rat

testes to gamma rays (9 Gy) resulted in no change in testosterone levels of

leydig cells Also Lambrot et al (2007) stated that low dose of radiation

(01Gy- 02Gy) had no effect on testosterone secretion or on the expression

of steroidogenic enzymes by leydig cell

El-Dawy and Ali (2004) stated that exposures of animals to gamma

irradiation resulted in a significant decrease in testosterone compared to

control

SivaKumar et al (2006) stated that therapeutic accidental and

experimental radiation decreased serum testosterone in male leading to

various sexual problems Also Eissa and Moustafa (2007) indicated that

doses of (3 Gy and 6 Gy) gamma radiation have testicular toxic effects in

rats


١٧

2110 Effects of ionizing radiation on antioxidant defensive

status Antioxidants are the bodys primary defense against free radicals and

reactive oxygen species (ROS) Free radicals can cause tissue damage by

reacting with polyunsaturated fatty acids in cellular membrane nucleotides

in DNA and critical sulfhydryl bonds in protein The over production of

ROS in both intra and extra spaces upon exposure of living subjects to

certain chemicals radiation or local tissue inflammation results in

oxidative stress defined as the imbalance between pro-oxidation and

antioxidants As a result of these imbalance free radicals a chain of lipid

peroxidation is initiated which induced cellular damage (Dasgupta et al

1997)

Exposure of the body to ionizing radiation produces reactive oxygen

species (ROS) that damage protein lipids and nucleic acids Because of the

lipid component in the membrane lipid peroxidation is reported to be

particularly susceptible to radiation damage (Rily 1994 Chevion et al

1999)

Radiation damage in cell is known to involve the production of free

radicals such as superoxide radical hydroxyl radical lipid radical and lipid

peroxide radical which produces lipid peroxide in biomembrane which

will develop various episodes of biohazarddous besides direct damage to

DNA Naturally existing scavenger system ie superoxide dismutase

catalase metallothioneins and glutathione peroxidase system work to

quench these oxidized substances (Matsubara et al 1987a)

Chen et al (1997) reported that free radicals resulting from exposure

to radiation accompanied by a decrease of glutathione peroxidase catalase

and superoxide dismutase (SOD) while Benderitter et al (2003) observed


١٨

an increase of malondialdhyde (MDA) in few hours after radiation

exposure The cells natural enzymatic and antioxidant mechanisms may be

the main cause of irradiation-induced peroxidation and damage to cell

activities

Glutathione (GSH) is the most abundant non-proteinthiol in

mammalian cells It plays an important role in regulation of cellular redox

balance The most recognized function of GSH is its role as a substrate for

glutathione S-transferase and GSH-peroxidase These enzymes catalyze the

antioxidant of reactive oxygen species (ROS) and free radicals GSH

which plays an important role in the detoxification of reaction metabolites

of oxygen showed to be decreased in tissue or plasma of irradiated animals

(Ramadan et al 2001) On the other hand Saada et al (1999) reported a

significant increase in blood GSH level after gamma-radiation exposure

Whole body exposure of male rats to 7 Gy gamma irradiation increased

lipid per-oxidation in the liver resulting in biomembrane damage of sub-

cellar structures and release of their enzymes This is evidenced by increase

of thiobarbituric acid reactive substances (TBARS) in mitochondria

lysosomes and microsomes (Saada and Azab 2001)

Metallothionins (MTs) are proteins characterized by high thiol

content and it binds Zn and Cu It might be involved in the protection

against oxidative stress and can act as free radical scavengers (Morcillo et

al 2000) MTs are important compounds on reducing the efficiency of

zinc absorption at elevated zinc intakes (Davis et al 1998) MTs play a

protective role against the toxic effects of free radicals and electerophiles

produced by gamma radiation (Liu et al 1999) The hepatic and renal

MTs have been increased after whole body X-irradiation (Shiraishi et al

1986)


١٩

Furthermore the whole body gamma-irradiation induced MTs-

mRNA transcription protein expression and accumulation in liver but not

in kidney or spleen That implicates the organ specific resistance to

radiation induce cellular damage (Koropatnick et al 1989) MTs are

involved in regulation of zinc metabolism and since radiation exposure

induces lipid peroxidation and increases MTs synthesis hypothesized that

MTs may be involved in protection against lipid peroxidation MTs are

involved in the protection of tissue against various forms of oxidative

injury including radiation lipid peroxidation and oxidative stress (Kondoh

and Sato 2002) Induction of MTs biosynthesis is involved in protective

mechanisms against radiation injuries (Azab et al 2004)

Sridharan and Shyamaladevi (2002) reported that whole body

exposure of rats to gamma rays (35 Gy) caused increases in lipid peroxide

reduced glutathione and total sulphhydryl groups which may also be

increased probably to counteract the damages produced by lipid peroxides

The excessive production of free radicals and lipid peroxides might have

caused the leakage of cytosolic enzymes such as AST ALT LDH creatine

kinase and phosphatases

Abady et al (2003) revealed that changes in the content of

reduced glutathione (GSH) glutathione peroxidase (GSHpx) glucose-6-

phosphate dehydrogenase (G-6-PD) superoxide dismutase (SOD) and

catalase (CAT) in blood liver and spleen were evaluated in different rat

groups The results revealed that transient noticeable increase during the 1st

hour post-irradiation in the above mentioned parameters followed by

significant decrease recorded after 7 days Ramadan (2003) reported that

CdCl2 administration andor irradiation induced cellular damage indicated

by significant decrease in lactate dehydrogenase isoenzyme (LDH-X)


٢٠

glutathione level (GSH) and glutathione peroxidase enzyme activity

(GSHpx) as well as significant increase in malondialhyde (MDA) in

testicular tissues

Many studies showed previously that total body irradiation at dose

level of 8 Gy produces increased lipid peroxidation in several tissues and

body fluids and changes in antioxidant enzymes activities (Kergonou et

al 1981 Feurgard et al 1999 Sener et al 2003 Dokmeci et al

2004)

Zahran et al (2004) observed significant elevation in MDA level

and γ-GT activity level accompanied by reduced level in GSH content after

radiation exposure Also Badr El-din (2004) indicated that in the kidney

irradiation exposure (65 Gy) induced significant elevation in TBARS

depletion in GSH and significant reduction in SOD activity

AbdelndashFatah et al (2005) demonstrated that exposure to whole

body gamma irradiation dramatically decreased the GSH in the cystol

fraction from the first day after exposure whereas MDA increased

significantly after irradiation Moreover Nada and Azab (2005) showed

that in irradiated group exposure to fractionated whole body γ-irradiation

(15 Gy every other day up to a total dose of 75 Gy) resulted in significant

increases in TBARS concentrations in all tissues (liver kidney and spleen)

after all experimental period whereas GSH content were significantly

decrease in all examined tissues after the second experimental period

Moreover the concentration of MTs in different tissues subjected to that

study were significantly increased after 1 day and significantly decreased

after 10 days comparing with control rats These changes in MTs levels

were associated with significant changes in metals concentrations in

different investigated tissues


٢١

Dokmeci et al (2006) stated that there were significant increases in

plasma and liver malondialdehyde (MDA) with marked reduction in GSH

levels in liver of irradiated group compared with controls Tawfik et al

(2006c) and Srinvasan et al (2007) stated that a significant increase in

lipid peroxidation (LPO) levels was observed in gamma irradiated group

whereas a significant decrease in GSH content was recorded in liver of

gammandashirradiated group

Ali et al (2007) stated that whole body γ-irradiation (65 Gy)

strongly initiates the process of lipid peroxidation (LPO) as indicated by

the formation of TBARS in both blood and liver reduction in GSH and

increased the formation of nitric oxide (NO)

In irradiated animals the oxidative marker malondialdhyde (MDA)

was significantly increased in the liver while a marked decrease in hepatic

of glutathione (GSH) was demonstrated (El-Missiry et al 2007) Also

Nada (2008) showed that rats exposed to ionizing radiation at single dose

(65 Gy) revealed elevation of lipid peroxidation and metallothioneins

while a sharp drop in glutathione level were recorded

El-Tahawy et al (2008) found that whole body gamma irradiation

produced oxidative stress manifested by significant elevation in lipid

peroxides levels measured as (TBARS) associated with significant decrease

in the antioxidant enzymes as SOD and Catalase (CAT)

Fahim (2008) reported that in irradiated rats exposure to

fractionated rates whole body gamma irradiation (3X2 Gy) resulted in

significant increase in MTs malondialdhyde (MDA) and NO

concentrations concomitant with significant decrease in GSH content

GSHpx and SOD activities in the organs homogenates


٢٢

Goyal and Gehlot (2009) showed that whole body gamma-

irradiation (6 Gy) of mice resulted in a decrease in GSH and increase in

LPO in the liver and blood of irradiated control group Also Mansour and

El-Kabany (2009) reported that exposure of rats to gamma irradiation

(2Gy- 8Gy) induced an increased in lipid peroxides and a significant

decrease in glutathione content superoxide dismutase and catalase

22 Essential trace elements Essential trace elements of the human body include zinc copper

selenium chromium cobalt iodine manganese and molybdenum although

these elements account for only 002 of the total body weight they play

significant roles eg as active centers of enzymes or as trace bioactive

substances (Kodama 1996)

Basically an essential element is one that is uniquely required for

growth or for the maintenance of life or health (Takacs and Tatar 1987)

A deficiency of the element consistently produces a functional impairment

which is alleviated by physiological supplementation of only that element

A biochemical basis for the elements essential functions must be

demonstrated For trace metals this is often the identification of a unique

metalloenzymes which contains the metal as an integral part or as an

enzyme activator (Takagi and Okada 2001) An element is considered by

Mertz (1970) to be essential if its deficiency consistently results in

impairment of a function from optimal to suboptimal Cotzias (1967) stated

that the position more completely He maintains that a trace element can be

considered essential if it meets the following criteria (1) it is present in all

healthy tissues of all living things (2) its concentration from one animal to

the next is fairly constant (3) its withdrawal from the body induces

reproducibly the same physiological and structural abnormalities regardless


٢٣

of the species studied (4) its addition either reverses or prevents theses

abnormalities (5) the abnormalities induced by deficiency are always

accompanied by pertinent specific biochemical changes and (6) these

biochemical changes can be prevented or cured when the deficiency is

prevented or cured

Trace elements are constituents ofor interact with enzymes and

hormones that regulate the metabolism of much larger amounts of

biological substrates If the substrates are also regulator the effect is even

further amplified (Abdel-Mageed and Oehme 1990a)

Essential trace elements are specific for their in vivo functions they

cannot be effectively replaced by chemically similar elements The

essential trace metal or element interacts with electron donor atoms such as

nitrogen sulpher and oxygen the type of interaction depending on

configurational preferences and bond types Specificity of trace element

function is also promoted by specific carrier and storage protein such as

transferrin and ferritin for iron albumin and α-macroglobulin for zinc

ceruloplasmin for copper transmanganese for manganese and

nickeloplasmin for nickel The carrier proteins recognize and bind specific

metals and transport them to or store them at specific sites with the

organism (Vivoli et al 1995 Mensa et al 1995)

Heavy metals are known to markedly alter the metabolism and

function of some essential trace element such as copper zinc iron

calcium manganese and selenium by competing for ligands in the

biological system (Mahaffey et al 1981 Komsta-Szumska and Miller

1986) Such competition and the legand-binding may have adverse effects

on the disposition and homeostasis of essential trace elements


٢٤

The deficiency of trace elements may depress the antioxidant defense

mechanisms (Kumar and Shivakumar 1997) erythrocyte production

(Morgan et al 1995) and enhance lipid abnormalities (Vorman et al

1995 Lerma et al 1995 Doullet et al 1998) On the other hand the

toxicity of trace elements may induce renal liver and erythropiotic

abnormalities (Langworth et al 1992 Chmielnicka et al 1993

Farinati et al 1995)

221 Trace elements in radiation hazards

(Radiation protection and recovery with essential

metalloelements) Copper iron manganese and zinc are essential metalloelements as

are sodium potassium calcium magnesium chromium cobalt and

vanadium Like essential amino acids essential fatty acids and essential

cofactors (vitamins) these metal elements are required by all cells for

normal metabolic processes but cannot be synthesized in vivo and are

obtained by dietary intake The amount of copper iron manganese and

zinc found in adult body tissues and fluids correlate with the number and

kind of metabolic processes which require them (Lyengar et al 1978)

Recognizing that loss of enzyme activity dependent on essential

metalloelements may at least partially account for lethality of ionizing

radiation and that copper iron manganese and zinc-dependent enzymes

have roles in protecting against accumulation of O2 as well as facilitating

repair (Sorenson 1978) and may explain the radiation protection and

radiation recovery activity of copper iron manganese and zinc compounds

(Matsubara et al 1986) It was suggested that the interlukine-1 (IL-1)-

mediated redistribution of essential metalloelements have a general role in

the response to radiation injury These redistributions may also account for


٢٥

subsequent de novo synthesis of the metalloelement-dependent enzymes

required for biochemical repair and replacement of cellular and extra

cellular components needed for recovery from radiolytic damage

(Sorenson 1992) De novo synthesis of metalloelement-dependent

enzymes required for utilization of oxygen and prevention of O2

accumulation as well as for tissues repair processes including

metalloelement dependent DNA RNA repair are key to hypothesis that

essential metalloelement complexes prevent andor facilitate recovery from

radiation induced lesions (Berg 1989) It is widely common that

superoxide (O2 ) accumulation due to the lack of normal concentrations of

SODs reduction of O2 leading to relatively large steady state

concentrations of O2 or in appropriate release of O2 from oxygen activating

centers lead to formation of much more reactive oxygen radicals (Droumlg

2002) These more reactive oxygen radicals include singlet oxygen (O2)

and hydrogen peroxide produced as result of acid dependent self

disproportionate of O2 hydroxyl radical and hydroperoxyl radical (Fee and

Valentine 1977) Prevention of some of the potential pathological changes

associated with radiation has been attributed to the scavenging of these

oxygen radicals by SODs and catalase (Corey et al 1987 Bauer et al

1980 Halliwell and Gutteridge 1989)

2211 Role of zinc in radiation protection and recovery Zinc is known to serve as the active center of many enzymes It

protects various membranes system from per-oxidative damage induced by

heavy metals and high oxygen tension and stabilization of perturbations

(Micheletti et al 2001) The protective effects of zinc against radiation

hazards have been reported in many investigations (Markant and Pallauf

1996 Morcillo et al 2000) Zinc is an essential oligo element for cell

growth and cell survival (Norii 2008) The antioxidant role of zinc could


٢٦

be related to its ability to induce metallothioneins (MTs) (Winum et al

2007) Metallothioneins is a family of low molecular weight (about 6-7

KDa) cystein rich (30) intracellular proteins with high affinity for both

essential (zinc and copper) and non-essential (cadmium and mercury)

metals (Krezel and Maret 2008) There are four major isoforms of MTs

the MT-I and MT-II isoforms are expressed ubiquitously in most

mammalian organs and are regulated coordinately The MT-III and MT-IV

isoforms are expressed specifically in the brain and squamous epithelium

(Ono et al 1998) respectively In general the major biological function of

MTs is the detoxification of potentially toxic heavy metals ions and

regulation of the homeostatic of essential trace elements However there

are increasing evidences that MTs can reduce toxic effects of several types

of free radical including superoxide hydroxyl and peroxyl radicals (Pierrel

et al 2007) For instance the protective action of pre-induction of MTs

against lipid peroxidation induced by various oxidative stresses has been

documented extensively (Morcillo et al 2000 McCall et al 2000)

It has been observed that gamma irradiation can induce synthesis of

MTs protein in liver kidney and thymus in rats (Shiraishi et al 1986

Santon et al 2003) It has been reported that metallothionein protect from

DNA damage induced by ionizing radiation (El-Gohary et al 1998

Vukovic et al 2000 Cai and Cherian 2003) protect against oxidative

stresses (Thornally and Vasak 1985) increase the antioxidant properties

(Kang 1999) play important role in free radicals scavenging (Kumari et

al 1998) induce neuro-protection properties (Cai et al 2000) play an

important role in the genoprotection (Jourdan et al 2002) and prevention

of radiation induced dermatitis (Ertekin et al 2004)


٢٧

-Effect of γ-irradiation on Zn metabolism Bors et al (1980) found that when the liver of dogs was exposed to

ionizing radiation at 2 Gy Zn concentration of hepatic vein blood increased

immediately within 120 min Also Walden and Farkas (1984) found that

whole body X-irradiation induces an elevation of Zn protoprophyrin of

blood in mice and rats A possible explanation for the increased MTs in

liver and Kidney was suggested by Shiraishi et al (1985) where Zn

accumulated in these damaged tissues by irradiation thus stimulating the

induction of MTs synthesis

Kotb et al (1990) found that there is a significant reduction in the

concentration of Zn in kidney after 24 hrs heart and spleen after 3 days

following irradiation with doses between 10 and 25 rem This decrease was

followed up by a gradual increase of the concentrations of the elements

which exceeded the pre-irradiation level in most cases Nada et al (2008)

indicated that irradiation andor 1 4 dioxane induced increases in zinc in

liver spleen lung brain and intestine Similar observation was obtained by

many investigators (Yukawa et al 1980 Smythe et al 1982) who found

that gamma-irradiation induced an elevation of zinc in different organs

2212 Role of copper in radiation protection and recovery Copper is one of the essential trace elements in humans and

disorders associated with its deficiency and excess have been reported

(Aoki 2003) Copper in the divalent state (Cu2+) has the capacity to form

complexes with many proteins In a large number of cuproproteins in

mammals copper is part of the molecule and hence is present as a fixed

portion of the molecular structure These metalloproteins form an important

group of oxidase enzymes and include ceruloplasmin (Ferroxidase)

superoxide dismutase cytochrome oxidase lysyl oxidase dopamine beta-


٢٨

hydroxylase tyrosinase uricase spermine oxidase benzylamine oxidase

diamine oxidase and tryptophan 2 3dioxygenase (tryptophan pyrrolase)

The metalloprotein and metallothioneins binds a number of heavy metals

including copper Copper also complexes readily with L-amino acids

which facilitate its absorption from the stomach and duodenum (Irato et

al 1996) The importance of copper in the efficient use of iron makes it

essential in hemoglobin synthesis (Han et al 2008)

It has been reported that copper protect from DNA damage induced

by ionizing radiation (Spotheium-Maurizot et al 1992 Cai et al 2001)

copper play important role in the amelioration of oxidative stress induced

by radiation (Abou-Seif et al 2003ab) maintaining cellular homeostasis

(Iakovelva et al 2002) and enhancement of antioxidant defense

mechanisms (Svensson et al 2006 Houmlrnberg et al 2007)

-Effect of γ-irradiation on Cu metabolism Kotb et al (1990) observed that 24 hrs after irradiation disturbances

in mineral elements (Cu Zn Fe Mg and Ca) were quite evident They

were manifested as reduced copper concentration in spleen heart and

kidney On the other hand Tamanoi et al (1996) found that after X-rays

whole body irradiation Cu increased from the 2nd day post-irradiation

Isoherranen et al (1997) reported that (ultra violet beam) UVB

irradiation reduced both the enzymatic activity and the expression of the

07 and 09 Kb mRNA transcripts of Cu-Zn SOD an antioxidant enzyme

Nada et al (2008) found that irradiation dose (65 Gy) andor 1 4

dioxane induced depression in copper levels in all studied organs liver

kidney spleen brain lung and intestine Similar observation were obtained

by many investigators (Yukawa et al 1980 Smythe et al 1982 Kotb et


٢٩

al 1990) who recorded that radiation induced decrease in copper in liver

heart and the spleen 2213 Role of iron in radiation protection and recovery Iron is the most important of the essential trace metals An

appreciable number of human diseases are related to iron deficiency or

disorders of iron metabolism (Kazi et al 2008) Blood iron is mainly

represented by hemoglobin and transferrin in a ratio of 1000 1 and by

ferritin in human serum and leukocytes It plays a role in iron transportation

and in the body defense mechanism against infection (Siimes et al 1974)

Serum ferritin is increased in liver disease and in leukemia (Worwood et

al 1974) Iron is involved in terminal oxidases and respiratory proteins

(Wang et al 2007) Cytochrome C oxidase is the terminal enzyme system

of the electron transport chain that contains two heme groups and two

copper ions In collagen synthesis the hydroxylation of proline and lysine

require iron as Fe (II) Heme enzymes (iron protoporphyrin) decompose

hydrogen peroxide to oxygen and water as in catalase or to water and

dehydrogenated product as with the peroxidases (Prockop 1971)

Hemopexin and hepatoglobin are glycoproteins secreted by the liver

Following intravascular hemolysis hemopexin binds heme and

hepatoglubin binds hemoglobin to the liver for catalysis and iron

conservation a process that is receptor mediated (Higa et al 1981)

A part from its involvement in heme synthesis iron is required in

many other biochemical processes ranging from oxidative metabolism to

DNA synthesis and cell division (Crowe and Morgan 1996) It has been

reported that iron and its complexes protect from ionizing radiation

(Sorenson et al 1990) play important role in facilitation of iron

dependent enzymes required for tissue or cellular repair processes


٣٠

including DNA repair (Greenberg et al 1991 Ambroz et al 1998)

protect against radiation induced immunosuppressant (Hunt et al 1994

Tilbrook and Hider 1998) and perhaps gene regulating proteins which

may ultimately account for its mechanism of action as a radiorecovery

agent (Basile and Barton 1989 Abou-Seif et al 2003b)

-Effect of radiation on iron metabolism Kotob et al (1990) reported that accumulation of iron in the spleen

could be resulted from disturbances in the biological function of RBCs

including possible intravascular haemolysis and subsequent storage of iron

in the spleen Crowe and Morgan (1996) have examined the uptake of

radiation transferring and radioactive iron into the brain of rats made iron

deficient in utero and also later in life They also demonstrated that both

iron and transferrin transport into the brain was more active in iron

deficient rats than in those fed adequate amount of iron

Tamanoi et al (1996) found that in X-ray irradiated mice iron

decreased from the 1st day Cu increased from the 2nd day while Zn and Ni

showed intensely down and rise in amount Brenneisen et al (1998)

studied a central role of ferrous ferric iron in the UVB irradiation and they

identified the iron driven fenton reaction and lipid peroxidation as possible

central mechanisms underlying signal transduction of the UVB response

In irradiated animals the iron was increased in liver and spleen

while a decrease in kidney lung intestine and brain was demonstrated

(Nada et al 2008) These observations are in full agreement with those of

Ludewig and Chanutin (1951) Heggen et al (1958) Olson et al (1960)

and Beregovskaia et al (1982) who reported increase of iron in liver and

spleen after whole body gamma-irradiation


٣١

2214 Role of selenium in radiation protection and recovery All cells in the body including the immune system cells require

adequate levels of nutrients for optimal performance Certain disease

conditions like infections with the associated immune system activation

may increase nutrinal requirements (Mudgal et al 2008) Even in the

absence of disease Se supplementation at or above the recommended level

seems to increase the function of some arms of the immune defense

including naiumlve lymphocyte (NL) cell activity in the spleen (EL-Sherbiny

et al 2006) Selenium deficiency leads to variety of diseases in humans

and experimental animals such as coronary artery diseases cardio-

myopathy atherosclerosis (Saloner et al 1988 Demirel-Yilmaz et al

1998) Se deficiency disturbs the optimal functioning of several cellular

mechanisms it generally impairs immune function including those defense

mechanisms that recognize and eliminate infection agents and increases

oxygen induced tissue damage (Taylor et al 1994 Roy et al 1993) It

has been established that the essential effects of selenium in mammals are

the result of several biologically active Se compounds They include the

family of glutathione peroxide GPX which are the classical GPXa plasma

GPX a GPX present predominantly in gastrointestinal tract and the

monomeric phospholipids hydroperoxide GPX (Sun et al 1998) A second

important enzymatic function of selenium was identified when types I II

and III iodothyrodinine diiodinases were identified as seleno-enzymes

(Croteau et al 1995)

Along with vitamin E seleno-glutathione peroxidase acts as part of

the antioxidant defense system of cells protecting lipids in cell membranes

from the destructive effects of H2O2 and superoxide anion (O2) generated

by excess oxygen (El-Masry and Saad 2005) It has been reported that

selenium play important roles in the enhancement of antioxidant defense


٣٢

system (Weiss et al 1990 Noaman et al 2002) increases resistance

against ionizing radiation as well as fungal and viral infections

(Knizhnikov et al 1991) exerts marked amelioration in the biochemical

disorders (lipids cholesterol triglycerides glutathione peroxidase

superoxide dismutase catalase T3 and T4) induced by free radicals

produced by ionizing radiation (El-Masry and Saad 2005) enhances the

radioprotective effects and reduces the lethal toxicity of WR 2721 (Weiss

et al 1987) protects DNA breakage (Sandstorm et al 1989) and

protects kidney tissue from radiation damage (Stevens et al 1989) Also

selenium plays important role in the prevention of cancer and tumors

induced by ionizing radiation (La Ruche and Ceacutesarini 1991 Chen

1992 Leccia et al 1993 Borek 1993) Selenium involved in the

deactivation of singlet molecular oxygen and lipid peroxidation induced by

oxidative stress (Scurlock et al 1991 Pietshmann et al 1992

Kandasamy et al 1993) Several orango-selenium compounds exhibiting

glutathione peroxidase activities were used as protective agents and exerted

hepatoprotective hem biosynthesis and bone marrow recoveries (Lata et

al 1993 Othman 1998 Yanardag et al 2001)

Selenium has been shown to counteract the toxicity of heavy metals

such as cadmium inorganic mercury methyl mercury thallium and silver

(Whanger 1992)

The presumed protective effect of Se against heavy metals toxicity is

through the diversion in their binding from low molecular weight proteins

to higher molecular weight ones Selenium reacts with mercury in blood

stream by forming complexes containing the two elements at an equimolar

ratio when selenit and mercuric chloride are co-administrated As the

distribution among the organs and sub- cellular localization of Hg are


٣٣

dramatically changed by the formation of the complex with selenium

(Yoneda and Suzuki 1997) Selenium is also effective in the prevention

of testicular injury induced by heavy metals (Niewenhuis and Fende

1978 Katakura and Sugawara 1999)

-Effect of γ-irradiation on Se metabolism Yukawa et al (1980) and Smythe et al (1982) studied the effect of

gammandashrays on distribution trace elements (Mg Se Zn Ca Fe amp Cu) in

various tissue bone heart aorta muscle liver kidney and lung They

found a significant increase of Ca Fe Zn and Mg in all organs and a

decrease of Cu and Se concentration in heart aorta and liver

ETHujić et al (1992) found that radiation induced a significant

decrease in selenium content and distribution in liver spleen heart and

blood and an increase in kidney testis and brain at a single dose 4 2 Gy

Nunes et al (2001) reported that ionizing radiation induced significant

decrease in Se content and distribution

2215 Role of calcium in radiation protection and recovery Calcium is essential for the functional integrity of the nervous and

muscular systems for normal cardiac function for conversion of

prothrombin into thrombin and as the major component of bone Ninety-

nine percent of total body calcium is found in bone and 1 is present in

serum Of the serum calcium 45 is bound to plasma protein and in active

the calcium in serves as a reservoir to maintain normal plasma calcium

levels (Kesler and Peterson 1985) Calcium absorption occurs in the

small intestine at a relatively steady rate of 30 of intake increasing to

approximately 50 during growth periods pregnancy and lactation An

acute calcium deficiency resulting in a plasma level below 80 mgdl results

in tetany (Lutwak et al 1974) chronic calcium deficiency results in


٣٤

osteoporosis or osteomalacia in adults and rickets in children (McCarter

and Holbrook 1992)

Many investigators found that nutrient extracts like curcumin

propolis and rosemary which contain highly contents of Ca Mg and Mn

exert benefit protect against radiation injury (Azab and Nada 2004 Nada

and Azab 2005 Nada 2008) Sorenson (2002) found that many calcium-

channel blockers drugs act as a radioprotection and radiorecovery prodrugs

-Effect of γ-irradiation on Ca metabolism Fauxcheux et al (1976) reported that the whole body gamma

irradiation caused disturbances and alteration in Ca level of the blood

Sarker et al (1982) exposed adult male rats to 4 and 10 Gy of whole

body X-rays plasma calcium level was studied on 1 3 and 6 days after

exposure The authors recorded that lethal radiation dose increased plasma

calcium initially Also a significant increase of Ca Fe Zn and Mg in

various tissues such as bone heart aorta muscle liver kidney and lung

and a decrease of Cu and Se concentrations in heart aorta and liver were

recorded by Yukawa et al (1980) and Smythe et al (1982)

Kotb et al (1990) observed a reduction in mineral elements

(copper zinc iron magnesium and calcium) in spleen heart and kidney 24

hrs after irradiation These organs showed different sensitivities to

irradiation El-Nimr and Abdel-Rahim (1998) found that exposure of rats

to gamma-irradiation (5 Gy) resulted in an increase of calcium in lung

liver spleen and kidney


٣٥

2216 Role of magnesium in radiation protection and

recovery Magnesium is a mineral acting primarily as an intracellular ion Over

the past decade clinical epidemiological and experimental data suggest

that magnesium the fourth most abundant cation in the human body plays

an important role in blood pressure control (Loyke 2002) According to

McSweeney (1992) the average adult body contains approximately 1000

mmol (2000 mEq) of Mg 99 of which is in bone and the intracellular

compartment of the 1 remaining in the vascular space 25 is bound to

proteins and it is ionized 75 that exerts the physiological effects with

calcium potassium magnesium regulates neuromuscular excitability and

conduction in the cell membrane It also has a role in the release of

parathyroid hormone Large loads of Mg can be excreted easily by the

kidneys hypermagnesemia usually appears with hypokalcemia calcemia

and phosphatemia Mgs effect on the vasculature is opposite to Ca (Lim

and Herzog 1998) Magnesium is found primarily intracellulary unlike

calcium which is extracelluar In hypertension intracellular free Mg is

deficient while calcium is elevated (Lim and Herzog 1998) The

deficiency of magnesium may depress the antioxidant defense mechanisms

(Kumar and Shivakumar 1997) erythrocyte production (Morgan et al

1995) increase cholesterol triglyceride phospholipids concentration lipid

peroxidation transaminases Fe and Ca in tissue (Vormann et al 1995

and Lerma et al 1995)

-Effect of γ-irradiation on Mg metabolism

Yukawa et al (1980) and Smythe et al (1982) studied the effect of

gamma-rays on distribution of trace elements (Mg Se Zn Ca Fe and Cu)

in various tissue bone heart aorta muscle liver kidney and lung They


٣٦



Kotb et al (1990) and Hawas (1997) found that reduced

concentration of Mg level in heart and elevation of Mg in plasma after

irradiation with 6 Gy while Nada et al (2008) found that irradiation

doesnt alter the level of Mg in some organs (liver brain)

2217 Role of manganese in radiation protection and

recovery Manganese is a cofactor for a number of enzymes including

argginase cholinesterase phosphoglucomutase pyruvate carboxylase

mitochondrial superoxide as well as several phosphatases peptidase and

glycosyl transferases (Pierrel et al 2007) Natural antioxidant enzymes

manufactured in the body provide an important defense against free

radicals Glutathione peroxidase glutathione reductase catalase

superoxide dismutase heme oxygenase and biliverdin reductase are the

most important antioxidant enzymes (Stocker and Keaney 2004) The

enzyme superoxide dismutase converts two superoxide radicals into one

hydrogen peroxide and one oxygen The superoxide dimutase molecule in

the cytoplasm contains copper and zinc atoms (CuZn-SOD) whereas the

SOD in mitochonderia contains manganese (Mn-SOD) (Beyer et al

1991) Manganese containing SOD is largely located in the mitochondria

is cyanide insensitive and contributes 10 of total cellular activity

(Weisiger and Fridovich 1973) Removal of the manganese from the

active sites of Mn-SODs causes loss of catalytic activity the manganese

cannot usually be replaced by other transition metals ion to yield functional

enzymes However if the supply of copper is restricted in Cu-Zn SOD


٣٧

more Mn-SOD is synthesized to maintain the total cellular SOD activity

approximately constant (Pasquier et al 1984)

Manganese plays important roles in de novo syntheses of

metalloelement dependent enzymes required for utilization of oxygen and

prevention of O accumulation as well as tissue repair processes including

metalloelement-dependent DNA and RNA repair are key to the hypothesis

that essential metalloelement chelates decrease andor facilitate recovery

from radiation-induced pathology (Sorenson 2002) It has been reported

that manganese and its compounds protect from CNS depression induced

by ionizing radiation (Sorenson et al 1990) effective in protecting against

riboflavin-mediated ultraviolet phototoxicity (Ortel et al 1990) effective

in DNA repair (Greenberg et al 1991) radiorecovery agent from

radiation induced loss of body weight (Irving et al 1996) radioprotective

agent against radiation increase lethality (Sorenson 2001 Sorenson et al

1990 Hosseinimehr et al 2007) manganese can be considered as

therapeutic agent in treatment of neuropathies associated with oxidative

stress and radiation injury (Mackenzie et al 1999) effective in recovery

from radiation induced skin and intestinal inflammation (Murata et al

1995 Gurbuz et al 1998) enhancement the induction of metallothionein

synthesis (Shiraishi et al 1983) overcoming inflammation due to

radiation injury (Booth et al 1999) and maintaining cellular homeostasis

(Iakovelva et al 2002 Abou-Seif et al 2003b) Manganese was also

reported to prevent the decrease in leukocytes induced by irradiation

(Matsubara et al 1987b)

-Effect of γ-irradiation on Mg metabolism Nada and Azab (2005) reported that irradiation induced a

significant decrease in Mn in liver and other organs


٣٨

23 Role of medicinal plants in radiation recoveries The use of plants is as old as the mankind Natural products are

cheap and claimed to be safe They are also suitable raw material for

production of new synthetic agents Medicinal plants play a key role in the

human health care About 80 of the world population relies on the use of

traditional medicine which is predominantly based on plant material

(WHO 1993)

Scientific studies available on a good member of medicinals

indicated that promising phytochemicals can be developing for many health

problems (Gupta 1994) There is at present growing interest both in the

industry and in the scientific research for aromatic and medicinal plants

because of their antimicrobial and antioxidant properties Herbs and spices

are amongst the most important targets to search for natural antimicrobials

and antioxidants from the point of view of safety (Ito et al 1985) So far

many investigations on antimicrobial (Beuchat 1994 Velluti et al 2003

Singh et al 2004) and antioxidant properties of spices volatile oils and

extracts have been carried out

Many antioxidant compounds naturally occurring from plant

sources have been identified as free radical or reactive oxygen scavengers

(Yen and Duh 1994 Duh 1998) Recently interest has increased

considerably in finding naturally occurring antioxidant for use in foods or

medicinal materials to replace synthetic antioxidants which are being

restricted due to their side effects such as carcinogenicity (Ito et al 1983

Zheng and Wang 2001) Natural antioxidants can protect the human body

from free radicals and retard the progress of many chronic diseases as well

as retard lipid oxidative rancidity in foods (Pryor 1991 Kinsella et al

1993 Lai et al 2001) Plant tissue is the main source of α- tochopherol


٣٩

ascorbic acid caratenoids and phenolic compounds (Kanner et al 1994

Weinberg et al 1999) Flavonoids and other plant phenolics have been

reported to have multiple biological effects such as antioxidant activity

anti-inflammatory action inhibition of platelet aggregation and

antimicrobial activity (Bors and Saron 1987 Moroney et al 1988 Pratt

and Hudson 1990 Van-Wauwe and Goossens 1983)

Over the past few years a number of medicinal plants have been

investigated for there quenching activity of specific reactive oxygen species

(ROS) such as hydroxyl radical the superoxide anion singlet oxygen and

lipid peroxides (Masaki et al 1995 Yen and Chen 1995) A high

correlation has been found between the amounts of polyphenolic

compounds as well as essential trace elements in plant materials and their

antioxidant activity

Fig 1 Foeniculum vulgare Mill

Bulb flower and seeds (Franz et al 2005)




and seed (fruits) of the plant are edible (fig1) Foeniculum vulgare is an

aromatic herb whose fruits are oblong ellipsoid or cylindrical straight or


٤٠

slightly curved greenish or yellowish brown in color The dried aromatic

fruits are widely employed in culinary preparations for flavoring bread and

pastry in candies and in alcoholic liqueurs as well as in cosmetic and

medicinal preparations (Farrell 1985 Haumlnsel 1993) Steam distillation of

dried fruits yields an essential oil referred as fennel oil used in western

countries for flavoring purposes (Husain 1994)

231 Chemical constituents of fennel Much work has recently been done on the yield and composition of

both extracts and volatile oils (essential) of fennel of several varieties from

several locations (Gupta et al 1995) Trans-anethole (1-methoxy-4-(1-

propenyl) benzene or para-propenylanisole) fenchone and estragole (fig 2)

are the most important volatile components of Foeniculum vulgare volatile

oil (Parejo et al 2004 Tognolini et al 2006)

Volatile components of fennel seed extracts by chromatographic

analysis include transe-anethole (50-80) fenchone (5) estragol

(methyl chavicol) safrol limonene 5 α-pinene 05 camphene β-

pinene β-myrcene α- phellandren P- cymene 3-carnene camphor and cis-

anethole (Simandi et al 1999 Ozcan et al 2001)

a b

Fig 2 Chemical Structure of fennel trans-anethole (a) estragole (b) and fenchone(c) (Bilia et al 2000

Fang et al 2006)


٤١

The seed of fennel contain approximately 20 of fatty oil of which

about 80 is petroselinic acid petroselinic acid (C181) is characteristic

fatty acid of family umbellifera and particularly of fennel oil Levels as

high as 70-80 has been recorded (Charvet et al 1991) This acid is of

interest because of its antimicrobial activity and because of its oxidation

gives lauric acid (C120) a very important fatty acid used in the soap

cosmetic medical and perfume industries and adipic acid (C60)

Petroselinic acid and oleic acid are always combined in umbelliferous oils

232 Absorption metabolism and excretion After oral administration of radioactively-labeled trans-anethole (as

the methoxy-14C compound) to 5 healthy volunteers at dose levels of 1 50

and 250 mg on separate occasions it was rapidly absorbed 54-69 of the

dose (detected as 14C) was eliminated in the urine and 13-17 in exhaled

carbon dioxide none was detected in the faces The bulk of elimination

occurred within 8 hours and irrespective of the dose level the principal

metabolite (more than 90 of urinary 14C) was 4-methoxyhippuric acid

(Caldwell and Sutton 1988) Trans-anethole is metabolized in part to the

inactive metabolite 4-methoxybenzoic acid (Schulz et al 1998) An earlier

study with 2 healthy subjects taking 1 mg of trans-anethole gave similar

results (Sangster et al 1987) In mice and rats trans-anethole is reported

to be metabolized by O-demethylation and by oxidative transformation of

the C3-side chain After low doses (005 and 5 mgkg body weight (bw)

O-demethylation occurred predominantly whereas higher doses (up to

1500 mgkg bw) gave rise to higher yields of oxygenated metabolites

(Sangster et al 1984ab)


٤٢

233 Mechanism of action

Fig 3 The putative mechanisms of radioprotection by

various plants and herbs (Jagetia 2007) Ionizing radiations induce reactive oxygen species in the form of

OH H singlet oxygen and peroxyl radicals that follows a cascade of

events leading to DNA damage such as single- or double-strand breaks

(DSB) base damage and DNA-DNA or DNA-protein cross-links and

these lesions cluster as complex local multiply damaged sites (Tominaga

et al 2004) The DNA-DSBs are considered the most lethal events

following ionizing radiation and has been found to be the main target of

cell killing by radiation The radioprotective activity of plant and herbs

may be mediated through several mechanisms since they are complex

mixtures of many chemicals (Yen and Duh 1994 Duh 1998) The

majority of plants and herbs contain polyphenols scavenging of radiation-

induced free radicals and elevation of cellular antioxidants by plants and

herbs in irradiated systems could be leading mechanisms for

radioprotection (Bors and Saron 1987 Moroney et al 1988 Pratt and

Hudson 1990 Van-Wauwe and Goossens 1983) The polyphenols


٤٣

present in the plants and herbs may up-regulate mRNAs of antioxidant

enzymes such as catalase glutathione transferase glutathione peroxidase

superoxide dismutase and thus may counteract the oxidative stress-induced

by ionizing radiations Up-regulation of DNA repair genes may also protect

against radiation-induced damage by bringing error free repair of DNA

damage Reduction in lipid peroxidation and elevation in non-protein

sulphydryl groups may also contribute to some extent to their

radioprotective activity The plants and herb may also inhibit activation of

protein kinase C (PKC) mitogen activated protein kinase (MAPK)

cytochrome P-450 nitric oxide and several other genes that may be

responsible for inducing damage after irradiation (Jagetia 2007)

234 Biological efficacy of Foeniculum vulgare essential oil In traditional medicine fennel and its herbal drug preparations are

used for dyspeptic complaints such as mild spasmodic gastric intestinal

complaints bloating and flatulence (Oumlzbek et al 2003) The medicinal

use of fennel is largely due to antispasmodic secretolytic secretomotor and

antibacterial effects of its essential oil

Many investigators have shown Foeniculum vulgare Mill extracts

and essential oil induced hepatoprotective effects (Oumlzbek et al 2004)

exhibited inhibitory effects against acute and subacute inflammatory

diseases and allergic reactions and showed a central analgestic effect (Choi

and Hwang 2004) produced antioxidant activities including the radical

scavenging effects inhibition of hydrogen peroxides H2O2 and Fe2+

chelating activities (EL-SN and KaraKaya 2004) increased gastric acid

secretion (Vasudevan et al 2000 Iten and Saller 2004) exerted

hypoglycemic effect (Oumlzbek et al 2003) exerted hypotensive properties

increased water sodium and potassium excretion suggesting that it has not


٤٤

a vascular relaxant activity but it appeared to act mainly as a diuretic and a

natriuretic (El-Baradai et al 2001) have estrogenic activities increase

milk secretion promote menstruation facilitate birth alleviate the

symptoms of the male climacteric and increase libido (Albert-Puleo

1980) and increase genital organs seminal vesicles lead to vaginal

cornification and oestrus cycle increase mammary gland oviduct

endometrium myometrium cervix and vagina (Malini et al 1985) It also

have properties for the prevention and therapy of cancer (Aggarwal and

Shishodia 2006 Aggarwal et al 2008) antitumor activities in human

prostate cancer (Ng and Figg 2003) antiviral properties (Shukla et al

1988) acaricidal activities (Lee 2004) antifungal (Mimica-Dukic et al

2003) and antimicrobial properities (Soylu et al 2006) Furthermore

fennel has a bronchodilatory effect that doesnt appear to be related to an

inhibitory effect on calcium but suggest a potassium channel opening

(Boskabady et al 2004) and Repellent properties (Kim et al 2004) as

well as immunomodulatory activities by enhancing natural killer cell

functions the effectors of the innate immune response (Ibrahim 2007ab)

The herb fennel (Foeniculum vulgare) is known for its protective

effect against toxins and has antioxidant and antibacterial activities A

study proved that there is a protective effect of Foeniculum vulgare

essential oil against the hepatotoxicity in the liver (Oumlzbek et al 2003)

Another study showed that the essential oil of FV beside other compounds

has been used to reduce oxidative stress in cardiovascular diseases (Cross

et al 1987)

Oktay et al (2003) showed that the water and ethanol extract of

fennel seeds showed strong antioxidant activity Both extracts of fennel

seeds (FS) have potential reducing power and are effective in free radical


٤٥

scavenging superoxide radical scavenging and hydrogen peroxide

scavenging and have metal chelating activities Foeniculum vulgare also

has anti-hepatotoxicity which proved by Oumlzbek et al (2004) who showed

that the hepatotoxicity produced by chronic carbon tetrachloride

administration was found to be inhibited by Foeniculum vulgare essential

oil with evidence of decreased levels of AST ALT ALP and bilirubin

Singh et al (2006) showed that both volatile oil and extract showed

strong antioxidant activity Toda (2003) revealed that several aromatic

herbs including Foeniculi Fructus have inhibitory effects on lipid

peroxidation or protein oxidative modification by copper Kaneez et al

(2005) stated that fennel extract attenuated the toxic effect of DDC

(Diethyldithiocarbamate) through reducing GPT levels and ameliorating

the effect of DDC on hepatic glutathione content

Choi and Hwang (2004) showed that Foeniculum vulgare

methanolic extract increased the plasma SOD catalase activities and high

density lipoprotein- cholesterol levels On the contrary the malodialdhyde

(MDA) (as a measure of lipid peroxidation) level was significantly

decreased FV has clearly protective effect against ethanol induced gastric

mucosal lesion and this effect at least in part depends upon the reduction

of lipid peroxidation and augmentation in the antioxidant activity (Birdane

et al 2007)

Tognolini et al (2007) stated that Foeniculum vulgare essential oil

and its main component anethole demonstrate a safe antithrombotic

activity that seems due to their broad spectrum antiplatelets activity clot

destabilizing effect and vaso-relaxant action Faudale et al (2008)

mentioned that fennel was found to exhibit a radical scavenging activity as

well as a total phenolic and total flavonoid content


٤٦

Nickavar and Abolhasani (2009) showed that ethanol extracts from

seven Umbellifera fruits including (Foeniculum vulgare) have antioxidant

activities


٤٧


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Aim of the work

٤٧

At this time we know very little regarding the effect of Foeniculum

vulgare Mill extracts and oils and their clinical applications in human

health and diseases The present study aims to elucidate the biochemical

effects of whole body gamma irradiation (65 Gy) on male rats and to

investigate the possible protective role of Foeniculum vulgare essential oil

(FEO) against gamma irradiation-induced biochemical changes in rats

Transaminases (AST and ALT) alkaline phosphatase (ALP) bilirubin

protein profile (total protein albumin globulin and AG ratio) cholesterol

(Ch) triglycerides (TG) urea creatinine and testosterone were assayed in

serum The antioxidant status glutathione reduced (GSH) and

metallothioneins (MTs) as well as the concentration of thiobarbituric acid

reactive substances (TBARS) were assayed in liver and kidney tissues

Also the present study is devoted to throw more light on the essential trace

elements (Fe Cu Zn Mg Ca Mn and Se) changes induced by Gamma

radiation in different studied tissue organs (liver spleen kidney and testis)

and the possible ameliorating effect of FEO in the modulation of these

alteration induced by gamma irradiation

Materials amp Methods

٤٨

41 Materials 411 Experimental animals

Male Swiss albino rats (Sprague Dawely Strain) weighting 120-

150 g were obtained from the Egyptian Organization for Biological

Products and Vaccines They were kept for about 15 days before the onset

of the experiment under observation to exclude any intercurrent infection

and to acclimatize the laboratory conditions The animals were kept in

metal cages with good aerated covers at normal atmospheric temperature

(25+5˚c) and at normal daily 12 hrs darklight cycles They were fed

commercial food pellets and provided with tap water ad libitum

412 Radiation processing

Whole body gamma irradiation performed with a Canadian gamma

cell 40-Cesium 137 biological sources belonging to the National Center

for Radiation Research and Technology (NCRRT) at Cairo Egypt The

radiation dose level was 65 Gy

413 Treatment

Fennel oil was purchased from local market (EL CAPTAIN

pharmaceutical Co) it was supplied to certain groups of animals as a single

dose (250 mgkg bw) according to Oumlzbek et al (2003) by intragastric

gavages

414 Sampling

4141 Blood samples

At the end of the experiment animals were subjected to diethyl ether

anesthesia Blood samples were collected left for 1 hr at room temperature


٤٩

and then centrifuged at 3000 rpm for 15 minutes to separate serum which

was kept at -20˚c till used for biochemical determination

4142 Tissue sampling

Immediately after the animals were sacrificed liver spleen kidney

and testis of each animal were quickly excised washed with normal saline

blotted with filter paper weighted and were placed in ice-cold saline (09 N

NaCl) and homogenized The homogenate was centrifuged at 10000 rpm

for 10 min at 4˚c using cooling centrifuge and the supernatant was

prepared for analysis

415 Chemicals 1 Alanine aminotransferase kit (Biodiagnostic)

2 Albumin kit (Spineract Spain)

3 Alkaline phosphatase kit (Biodiagnostic Egypt)

4 Aspartate aminotransferase Kit (Biodiagnostic Egypt)

5 Bilirubin (Total) kit (Diamond Egypt)

6 Cholesterol kit (Biodiagnostic Egypt)

7 Creatinine kit (Biodiagnostic Egypt)

8 Glycine (Sigma Egypt)

9 Hydrochloric acid (HCL) (Merck Germany)

10 N-butyl alcohol (Merck Germany)

11 Potassium chloride (KCL) (El Nasr Egypt)

12 Potassium dihydrogen Phosphate (El Nasr Egypt)

13 Reduced glutathione (Biodiagnostic Egypt)

14 Silver nitrate (AgNO3) (El-Nasr Egypt)

15 Sodium chloride (NaCl) (Sigma Egypt)

16 Sodium dibasic phosphate (El-Nasr Egypt)

17 Sodium hydroxide (NaOH) (Sigma Egypt)


٥٠

18 Thiobarbityric acid (TBA) (Sigma USA)

19 Trichloroacetic acid (TCA) (Sigma USA)

20 Triglyceride Kit (Biodiagnostic Egypt)

21 Tris-hydrochloric acid (HCL) (Merk Germany)

22 Total protein Kit (Spineract Spain)

23 Urea Kit (Biodiagnostic Egypt)

416 Apparatus 1 Microwave digistor sample preparation lab station MLS-1200 MEGA

Italy

2 SOLAR System Unicam 939Atomic Absorption Spectrometer England

3 ELGA Ultra pure water station England

4 Spectrometer Unicam 5625 UVVIS England

5 TRI-R STIR-R model K41 homogenizer

6 UNIVERSAL -16 R cooling centrifuge Germany

7 SELECTA UNITRONIC 320 OR water bath Spain

8 Mettler 200A analytical balance Switzerland

9 ELIZA plate reader Dynatechreg MR 2000 417 Experimental design (animal grouping)

After an adaptation period of one week the animals were divided

into four groups each of 8 rats

Group 1 normal control group (Non-irradiated)

Group 2 irradiated group (IRR)

The animals were subjected to a single dose of whole body gamma

irradiation (65 Gy) and were sacrificed after 7 days of irradiation

Group 3 treated group

The animals were received Foeniculum vulgare Mill essential oil

(FEO) (250 mgkg bwt) for 28 consecutive days through oral

administration by intra-gastric gavages


٥١

Group 4 administrated with FEO then exposed to radiation

The animals were received treatment FEO for 21 days then were

exposed to gamma radiation (65Gy) followed by treatment with FEO 7

days later to be 28 days as group 3

At the end of the experimental period animals in all groups were

sacrificed under diethyl ether anesthesia Blood samples were rapidly

obtained from heart puncture and animals were rapidly dissected for

excision of different organs

42 Methods 421 Assay of various biochemical parameters in serum 4211 Determination of alanine amino transferase (ALT) activity

The serum alanine aminotranseferase activity in the sample was

determined according to the method of Reitman and Frankel (1957) by

the kits obtained from Biodiagnostic Egypt

Principle

Colometric determination of ALT activity depending on the

following reaction-

glutamatepyruvate ateketoglutarαAlanine GPT +minus+ ⎯⎯rarr⎯

The keto acid pyruvate formed is measured in its derivative form 2

4-dinitrophenylhydrazone

4212 Determination of aspartate aminotransferase (AST) activity

The serum aspartate aminotranseferase activity in the sample was


the kit purchased from Biodiagnostic Egypt


٥٢

Principle

Colorimetric determination of AST activity depending on the

following reaction

glutamateteoxaloacetaateketoglutarαAspartate GOT +minus+ ⎯⎯ rarr⎯

The keto acid oxaloacetate formed is measured in its derivative form

2 4-dinitro-phenyl hydrazone

4213 Determination of alkaline phosphatase (ALP) activity

Alkaline phosphatase was determined by the method reported by

Belfield and Goldberg (1971) using ALP-kit obtained from

Biodiagonestic Egypt

Principle

The procedure depends on the following reaction

Phenylphosphate Phenol + PhosphateALP

pH 10

The liberated phenol is measured colorimetrically in the presence of

4-aminophenazone and potassium ferricyanide

4214 Determination of bilirubin activity (total)

Serum total bilirubin was determined by the method reported by

Balistreri and Shaw (1987) using bilirubin-kit obtained from

Diamond Company Egypt

Principle

The total bilirubin concentration is determined in presence of

caffeine by the reaction with diazotized sulphanic acid to produce an

intensely colored diazo dye (560-600nm) The intensity of color of this dye

formed is proportional to the concentration of total bilirubin

Diazotized Sulfanilic acid⎯⎯ rarr⎯HCLSulphanic acid +NaNO2


٥٣

Bilirubin + Diazotized Sulfanilic acid ⎯⎯ rarr⎯ 41PH Azobilirubin

4215 Determination of total protein concentration

Serum total protein concentration was determined according to the

method of Doumas et al (1971) using reagent kits purchased from

Spinreact Company (Spain)

Principle

Protein forms a colored complex with cupric ions in an alkaline

medium

4216 Determination of albumin concentration

Serum albumin concentration was determined according to the


Spinreact Company Spain

Principle

In a buffered solution bromocresol green forms with albumin a green

colored complex whose intensity is proportional to the amount of albumin

present in the specimen

4217 Determination of serum globulin concentration and

albuminglobulin (AG) ratio

Serum globulin concentration and albuminglobulin ratio were

measured and calculated according to Doumas et al (1971) from the

following equations

( )

Globulin (g L) Total proteins (g L) Albumin (g L)

Albumin globulin (A G) ratioAlbumin (g L)

Total proteins g L Albumin (g L)

= minus

=minus


٥٤

4218 Determination of urea concentration

Urea was determined according to the method reported by Fawcett

and Scott (1960) using reagent kit obtained from Biodiagnostic Egypt

Principle

The method is based on the following reaction

23Urease

2 CO2NH OHUrea ++ ⎯⎯ rarr⎯ The ammonium ions formed are measured by the Berthelot reaction

The blue dye indophenol product reaction absorbs light between 530 nm

and 560 nm proportional to initial urea concentration

4219 Determination of creatinine concentration

Serum creatinine concentration was determined according to the

method of Schirmeister et al (1964) using reagent kits obtained from

Biodiagnostic Egypt

Principle

Creatinine forms a colored complex with picrate in an alkaline medium

42110 Determination of cholesterol concentration

Serum cholesterol concentration was determined according to the

method reported by Richmond (1973) and Allain et al (1974) using

reagent kits purchased from Biodiagnostic Egypt

Principle

The cholesterol is determined after enzymatic hydrolysis and

oxidation The quinoneimine is formed from hydrogen peroxide and 4-

aminoantipyrine in the presence of phenol and peroxidase


٥٥

Esters cholesterol + H2Ocholesterol

esterase cholesterol + fatty acids

cholesterolesterasecholesterol + O2 cholest-4-en-one + H2O2

O4Hnequinoneimi yrine aminoantip4OH 2peroxidase

22 +⎯⎯⎯ rarr⎯minus+

42111 Determination of triglyceride concentration

Serum triglycerides concentration was determined according to the

method of Fossati and Principe (1982) using reagent kits purchased from

Biodiagnostic Egypt

Principle

The principle of the method depends on the following reactions

LHCO4H ine Quinoneim yrine Aminoantip4ol Chlorophen4O2H

OHphatecetonephosDihydroxya Phosphate3Glycerol

ADPPhosphate3Glycerol ATP Glycerol

fattyacidGlycerol desTriglyceri

2

Peroxidase22

Oxidase

22phosphate3Glycerol

aseGlycerokin

Lipase

++minus+minus+

+minusminus

+minusminus+

+

⎯⎯⎯ rarr⎯

⎯⎯⎯⎯⎯⎯ rarr⎯

⎯⎯⎯⎯ rarr⎯

⎯⎯ rarr⎯

minusminus

42112 Determination of serum testosterone concentration

Serum testosterone was determined in the sera by enzyme

immunoassay kit (Meddix Bioech Inc 420 Lincoln Centre Drive Foster

City CA 94404 USA Catalog Number KEF4057)


٥٦

422 Assay of different variables in tissue homogenate

4221 Measurement of lipid peroxidation (LPO)

The lipid peroxidation products were estimated as thiobarbituric acid

reactive substances (TBARS) according to Yoshioka et al (1979)

1 Weigh tissue and wash in saline

2 Homogenize in 4 volumes of 025 M sucrose

3 The homogenate is centrifuged at 2700 rpm for 15 min

4 A 05 of supernatant is shaken with 25 ml of 20 trichloroacetic

acid (TCA) in a 10 ml centrifuge tube

5 Add to the mixture 1ml of 067 thiobarbituric acid (TBA)

6 Shake and warm for 30 min in a boiling water bath followed by

rapid cooling

7 Then add 4 ml n-butyl alcohol and shake it

8 Centrifuge at 3000 rpm for 10 min

9 The resultant n-butanol layer is taken into a separate tube

10 Determine the MDA (Malonaldhyde bisndashdiethylacetate) from

absorbance at 535 nm by colorimetry

11 The standard used is 10 mmol MDA

12 Level of peroxidation products is expressed as the amount of MDA

per gm tissue

4222 Measurement of metallothioneins (MTs)

Metallothioneins was determined according to the method described

by Onosaka and Cherian (1982)

1 Weigh tissues and wash in saline

2 Homogenize in volume of sucrose solution (025 M)

3 Centrifuge the homogenate at 6000 rpm at 4˚c for 20 minutes

4 Store the aliquots at -20˚c until use


٥٧

5 Incubate 005 ml aliquote with 05 ml of (20 ppm Ag) for 10 minutes

at 20 ˚c (05 ml) (AgNO3 dissolved in deionized water)

6 The resulting Ag-MT incubated in 05 ml M glycine-NaOH buffer

(PH= 85) for 5 min

7 Excess Ag will removed by addition of 01 ml mutant RBCs

homolysate followed by heat treatment in boiling water bath for 15

min and centrifugate at 3000 rpm for 5 min

8 Repeat step 7 (hem treatment) twice to ensure the removal of

unbound metal Ag

9 Measurement of silver Ag in the supernatant which proportional to

the amount of metallothioneins

- Preparation of Rat or Mutton RBCs hemolysate

1 Blood is obtained from the abdominal aorta under diethyl ether

anesthesia into heparinized tubes

2 20 ml of 15 KCL added to 10 ml blood and mix well

3 Centrifuge at 3000 rpm for 5 min at 10˚c

4 The pellet containing the RBCs suspended in 30 ml 115 KCL and

centrifuge

5 Wash and centrifuge previous steps repeated twice

6 The washed RBCs suspend in 20 ml of 30 mM tris HCL buffer PH

80

7 Keep in room temperature 10 min for hemolysis and centrifuge at

3000 rpm for 10 min at 20˚c

8 The supernatant fraction is collected and used for the hemolysate

9 The hemolysat samples can be stored at 4˚c for 2-3 weeks


٥٨

4223 Glutathione reduced (GSH)

Glutathione reduced was determined according to the method

reported by Beutler et al (1963) using the kit obtained from Biodiagnostic

Egypt

Principle

The method is based on the reduction of 5 5 dithiobis (2-

nitrobenzoic acid) (DTNB) with glutathione (GSH) to produce a yellow

compound The reduced chromogen is directly proportional to GSH

concentration and its absorbance can be measured at 405 nm

423 ATOMIC ABSORPTION SPECTROPHOTOMETRY

4231 Theory The method used in the estimation is based on the fact that atoms of

an element in the ground or unexcited state will absorb light of the same

wave length that they emit in the excited state The wave length of that

light or the resonance lines is characteristic for each element No two

elements have identical resonance lines Atomic absorption

spectrophotometer involves the measurement of light absorbed by atoms in

the ground state It is different from flame photometry in that the later

employs the measurement of light emitted by atoms in the excited state

Most elements have several resonance lines but usually one line is

considerably stronger than the others The wave length of this line is

generally the one selected for measurement Occasionally however it may

be necessary to select another resonance line either to reduce sensitivity or

because resonance line of an interfering element is very close to the one of

interest (Kirbright and Sargent 1974)


٥٩

4232 Interference The most troublesome type of interference in atomic absorption is

usually termed chemical and is caused by lack of absorption of atoms

bound in molecular combination in the flame This phenomenon can occur

when the flame is not sufficiently hot to dissociate the molecule as in the

case phosphate interference with magnesium and calcium or because the

dissociated atom is immediately oxidized to a compound that will not

dissociate further at the temperature of the flame The addition of

lanthanum will overcome the phosphate interference in the magnesium and

calcium determination Ionization interferences occur when the flame

temperature is sufficiently high to generate the removal of an electron from

neutral atom giving a positively charged ion This type of interference can

generally be controlled by the addition to both standard and sample

solution of a large excess of an easily ionized element Spectral

interference can occur when an absorbing wavelength of an element

present in the sample but not being determined falls within the width of an

absorption line of the element of interest Spectral interference may

sometimes be reduced by narrowing the slit width (Cresser and Macleod

1976)

4233 Instrumentation

The selected elements were then estimated quantitatively by using

SOLAR System Unicam 939 Atomic Absorption Spectrometer equipped

with a deuterium background corrections fitted with GFTV accessory a

SOLAR GF 90 Grafite Furnce and SOLAR FS 90 plus Furnce Auto-

sampler The system was controlled by a SOLAR Data Station running the

SOLAR Advanced and QC software packages Hallow cathode lamps were

used to determine the following elements Fe Cu Zn Mn Ca Se and Mg

All solutions were prepared with ultra pure water within a specific


٦٠

resistivity of 182 M Ωcm-1 obtained from (ELGA Ultra Pure Water

Station England) deionizer feed water using Reverse Osmosis unit and

mixed bed ion exchanger thus removing most of the dissolved salts

Solutions prepared immediately before use Value of concentration of the

elements in each sample was calculated by the calibration curve method

using standard stock solutions (1000 microgml) for each studied element All

chemicals used were of analytical grade

The element concentration in the original sample could be

determined from the following equation

C1 microg X D

C2 microgg = (for solid sample) Sample weight

Where

C1 = metal concentration in solution

C2 = metal concentration in sample

D = dilution factor

C1 microg X D

C2 microg g = (for liquid sample) Sample volume

The results of the concentration of the studied elements calculated through

the solar data station


٦١

The samples were atomized under the instrumental conditions shown in

this table

Se Mg Ca Mn Zn Cu Fe Element 1960

05

15

4 sec

5

384

029

74

2855

05

2-3

4 sec

5

9-12

0003

013

4227

05

5-7

4 sec

5

4-44

0015

08

2795

05

5-7

4 sec

5

9-12

0029

057

2139

05

4-7

4 sec

5

9-12

0013

022

2139

05

2-4

4 sec

5

8-11

041

18

2483

02

7-11

4 sec

5

8-11

006

15

Wave length ( nm)

Band pass (nm)

Lamp current (mA)

Integration period

Air flow rate (Lm)

Acetylene flow rat

(Lm)

Sensitivity

Flame (mgL)

Furnace (pg)

4234 Sample preparation 42341 Tissue samples

Tissue samples were prepared by washing thoroughly with deionizes

water The weighted samples were digested in concentrated pure nitric acid

(65 ) (S G 142) and hydrogen peroxide in 14 ratios (IAEA 1980)

Sample digestion is carried out with acids at elevated temperature and

pressures by using microwaves sample preparation Labstation MLS-1200

MEGA Sample then converted to soluble matter in deionized water to

appropriate concentration level The studied elements were detected

quantitavely using standard curve method for each element (Kingston and

Jassie 1988)

42342 Microwave Digestor Technology

Microwave is electromagnetic energy Frequencies for microwave

heating are set by the Federal Communication Commission and

International Radio Regulations Microwave Frequencies designated for


٦٢

industrial medical and scientific uses The closed vessels technology

included by microwave heating gives rise to several advantages (1) Very

fast heating rate (2) Temperature of an acid in a closed vessel is higher than

the atmospheric boiling point (3) Reduction of digestion time (4)

Microwave heating raises the temperature and vapor pressure of the

solution (5) The reaction may also generate gases further increasing the

pressure inside the closed vessels This approach significantly reduces

overall sample prep Time and eliminates the need for laboratories to invest

in multiple conventional apparatuses (Vacum drying oven digestion

system and water or sanded baths) (Kingston and Jassie 1988) (IAEA

1980)

424 Statistical Analysis of Data

The data were analyzed using one-way analysis of variance

(ANOVA) followed by LSD test to compare various groups with each

others using PC-STAT program (University of Georgia) coded by Rao et

al (1985) Results were expressed as mean plusmn standard error (SE) and

values of Pgt005 were considered non-significantly different while those

of Plt005 and Plt001 were considered significant and highly significant

respectively F probability expresses the general effect between groups


٦٣


٦٤

Results

٦٣

1 Effect of Foeniculum vulgare essential oil on serum AST ALT and

ALP activities (Table 1 and Figure 4)

The results represented in table 1 and illustrated in figure 4 revealed

that whole body gamma irradiation at single dose (65 Gy) resulted in

significant elevation (LSD Plt001) in AST and ALP recording percentage

changes of 5064 and 3822 from the control level respectively

However gamma irradiation produced no significant (LSD Pgt005) effect

in ALT (517) in comparison with normal control

The prolonged administration of fennel oil (250 mgkg bwtday) for

28 consecutive days showed insignificant changes (LSD Pgt001) in

transaminases activities (AST ALT) and alkaline phosphatase (ALP) when

compared with control rats recording a percentage change of 101

358 and 257 from control level respectively

The supplementation of rats with fennel oil (250 mgkg bwt) for 21

successive days before irradiation and 7 successive days after whole body

gamma irradiation induced significant amelioration in the levels of the

above mentioned parameters as compared with irradiated rats These

improvements were manifested by modulating the increase in activities of

AST and ALP from 5064 and 3822 to 253 and 396 respectively

Regarding one-way ANOVA test the general effect in between

groups on AST and ALP activities was very highly significant (Plt0001)

while it was only significant on ALT activity through the experiment

Results

٦٤

Table 1 Effect of Foeniculum vulgare essential oil (FEO) on serum

AST ALT ALP activities in normal irradiated and treated rats

Parameters Groups

AST Ul

ALT Ul

ALP Ul

Control 5049plusmn 163b 2705plusmn 049ab 16741plusmn 359b

Irradiated (IRR) Ch of Control

7606plusmn 134a 5064

2845plusmn 05a 517

2314plusmn 46a 3822

Treated (FEO) Ch of Control

51plusmn 135b 101

2802 plusmn 052a 358

17201plusmn 334b 275

Irradiated + (FEO) Ch of Control

5177plusmn1103b 253

2577plusmn 095b

-473 17404plusmn 406b

396 F probability Plt0001 Plt005 Plt0001

LSD at the 5 level 397 187 1139


Values are expressed as mean plusmn SE of 8 observations Means which share the same superscript symbol(s) are not significantly different Pgt005 (1) If the difference between two means is higher than value of LSD at the 5 level the effect will be significant (Plt005) (2) If the difference between two means is higher than value of LSD at the 1 level the effect will be highly significant (Plt001)

Fig 4 Effect of FEO on liver functions of normal and irradiated rats

0

50

100

150

200

250

Control Irradiated Treated IRR+TR

Groups

Act

iviti

es (U

I)

AST ALT ALP

a

b b

a a b

b

a

b b

b

ab

Results

٦٥

2 Effect of Foeniculum vulgare essential oil on serum bilirubin in

normal irradiated and treated rats (Table 2 and Figure 5)


that whole body gamma irradiation at single dose (65 Gy) resulted in a

highly significant increase (LSD Plt001) in bilirubin recording percentage

changes of 2338 compared to the control level


28 consecutive days showed a non-significant change in serum bilirubin

level when compared with control rats recording a percentage change of

141 of the control level

The supplementation of rats with fennel oil for 21 successive days

before irradiation and 7 successive days after whole body gamma

irradiation induced significant amelioration in the level of bilirubin as

compared with irradiated rats These improvements were manifested by

modulating the increase in activities of bilirubin from 2338 to -535

respectively


groups on bilirubin activities was very highly significant (Plt0001) activity

through the experiment

Results

٦٦

Table 2 Effect of Foeniculum vulgar essential oil on serum bilirubin in normal and irradiated rats

Group Bilirubin (mgdl)

Control 177plusmn0074b


219plusmn0071a

2338 Treated (FEO) Ch of Control

180plusmn0055b

141 Irradiated +FEO Ch of Control

168plusmn0044b

-535 F probability Plt0001 LSD at the 5 level 0180

LSD at the 1 level 0243


Fig 5 Effect of FEO on serum bilirubin of normal and irradiated rats

0

05

1

15

2

25


Groups

Con

cent

ratio

n (m

gdl

)

Bilirubin

b

a

bb

Results

٦٧

3 Effect of Foeniculum vulgare essential oil on protein profile in




significant decrease (LSD Plt005) in total protein and albumin (LSD

Plt0001) recording percentage changes of -998 -1676 of the control

level respectively However gamma irradiation produced no significant

(LSD Pgt005) effect in globulin (093) and AG ratio (-479) in

comparison with normal control

The prolonged administration of fennel oil for 28 consecutive days

showed significant increase in total protein globulin significant decrease

in AG ratio and non-significant change in albumin when compared with

control rats recording a percentage change of 1016 3116 -2635

and -318 of control level respectively



gamma irradiation induced significant amelioration in the levels of total

protein and albumin as compared with irradiated rats These improvements

were manifested by modulating the decrease in activities of total protein

and albumin from -998 and -1676 to 285 and -983 respectively

Moreover there was an increase in globulin level with a percentage change

of 2325 of the control level


groups on total protein albumin globulin and AG ratio activities was very

highly significant (Plt0001) through the experiment

Results

٦٨

Table 3 Effect of Foeniculum vulgare essential oil (FEO) on protein profile activities in normal irradiated and treated rats

AG ratio Globulin

(gdl) Albumin

(gdl) T-proteins

(gdl) parameter

Groups 167plusmn 003a 215plusmn0065b 346plusmn006a 561plusmn 015b Control

159plusmn 005a

-479 217plusmn008b

093 288plusmn011c

-1676 505plusmn 019c

998- Irradiated (IRR) Ch of Control

123plusmn 003b

-2635 282plusmn012a

3116 335plusmn0073a

318- 618plusmn 020a


122plusmn 021b

-2695 265plusmn0104a

2325 312plusmn005b

-983 577plusmn 014ab

285 Irradiated + (FEO) Ch of Control

Plt0001 Plt0001 Plt0001 P lt0001 F probability 0107 0275 0225 0499 LSD at the 5level0144 0371 03039 0674 LSD at the 1level


Fig 6 Effect of FEO on protein profile in normal and irradiated rats

0

1

2

3

4

5

6

7

Contron Irradiated Treated IRR+TR

Groups

Con

cent

ratio

n(g

dl)

T-protein Albumin Globulin AG ratio

bc

a

ab

a

c

ab

b b

a a

a ab

b

Results

٦٩

4 Effect of Foeniculum vulgare essential oil on serum urea and

creatinine activities (Table 4 and Figure 7)

A Highly significant increase in urea and creatinine concentrations

was observed after exposure to whole body γ- irradiation (65 Gy)

recording percentage changes of 4601 and 5786 respectively

No appreciable changes were recorded in serum urea (-647) and

creatinine (645) concentrations of treated group with FEO (250 mgkg

bwday)

On the other hand group irradiated and treated with FEO exhibited a

highly significant decrease in urea and creatinine levels abnormalities

induced by irradiation compared with irradiated group It turned the value

of urea and creatinine levels almost to their normal values with percentage

change of -210 and 2830 from control respectively

Regarding one way ANOVA test the general effect between groups

was very highly significant (Plt0001) throughout the experiment

Results

٧٠

Table 4 Effect of Foeniculum vulgare essential oil (FEO) on serum urea and creatinine concentrations in normal irradiated and treated rats

Parameters Groups

Urea (mgdl)

Creatinine (mgdl)

Control 3569 plusmn 089b 0636 plusmn 0018c Irradiated (IRR) Ch of Control

5211 plusmn 146a 4601

1004 plusmn 006a 5786


3338 plusmn 101b 647-

0677 plusmn 057c 645


3494 plusmn 114b -210

0816 plusmn 16b

2830 F probability Plt0001 Plt0001 LSD at the 5 level 304 0093 LSD at the 1 level 4107 0125


Fig 7 Effect of FEO on serum urea and creatinine concentrations of normal and irradiated rats

0

10

20

30

40

50

60


Groups

Con

cent

ratio

ns (m

gdl

)

Urea Creatinine

b

a

bb

ca

cb

10

Results

٧١

5 Effect of Foeniculum vulgare essential oil on serum cholesterol and

triglyceride concentrations (Table 5 and Figure 8)

Whole body gamma irradiation of rats induced a highly significant

(LSD Plt005) elevation of cholesterol and triglycerides concentrations

recording percentage 12427 and 16367 in comparison with control

group

In contrast treatment with FEO produced non-significant (LSD

Pgt005) changes in cholesterol and triglyceride concentration when

compared with control group with a percentage change of 653 and -

316 respectively

Administration of fennel oil (FEO) produced a potential amelioration

of the elevated concentrations of cholesterol and triglycerides induced by

irradiation These ameliorations were manifested by modulating the

increase in cholesterol and triglycerides from 12427 and 16367 to

7117 and 3929 respectively


was very highly significant (LSD Plt0001) throughout the experiment

Results

٧٢

Table 5 Effect of Foeniculum vulgare essential oil (FEO) on serum cholesterol and triglycerides concentrations in normal irradiated and treated rats


Fig 8 Effect of FEO on cholesterol and triglyceride concentrations of normal and irradiated rats

0

20

40

60

80

100

120

140


Groups

Con

cent

ratio

ns (M

gdl

)

Cholesterol Triglyceride

c

a

c

b

c

a

c

b

Parameters Groups

Cholesterol mgdl

Triglycerides mgdl

Control 4166 plusmn 127c 4487 plusmn 172c Irradiated (IRR) Ch of Control

9343 plusmn 138a 12427

11831plusmn 18a 16367


4438 plusmn 14c 653

4345 plusmn 143c -316


7131 plusmn 113b

7117 625 plusmn 132b

3929 F probability Plt0001 Plt0001 LSD at the 5 level 365 460

LSD at the 1 level 493 621

Results

٧٣

6 Effect of Foeniculum vulgare essential oil on serum testosterone

concentration (Table 6 and Figure 9)



highly significant decrease (LSD Plt005) in testosterone recording

percentage change of -2325 as compared to control level Treatment

with fennel oil (250 mgkg bwtday) for 28 consecutive days (group 3)

showed a highly significant increase (LSD Plt001) in serum testosterone

when compared with control rats recording a percentage change of 6675

of control level respectively



gamma irradiation induced significant increase in the diminished levels of

testosterone of irradiated rats to reach a value above the control level by a

percentage change of 6500


groups on serum testosterone activities was very highly significant

(Plt0001) activity through the experiment

Results

٧٤


testosterone concentration in normal irradiated and treated rats

Testosterone (ngml) Group

400plusmn0086b Control

307plusmn0303c

-2325 Irradiated (IRR) Ch of Control

667plusmn025a


660plusmn009a

65 Irradiated + FEO Ch of Control

Plt0001 F probability0597 LSD at the 5 level 0805 LSD at the 5 level


Fig 9 Effect of FEO on serum testosterone concentration of normal and irradiated rats

0

1

2

3

4

5

6

7

8


Groups

Con

cent

ratio

n (n

gm

l)

Testosterone

b

c

a a

Results

٧٥

٧ Effect of Foeniculum vulgare essential oil on antioxidant status in

liver fresh tissues (Table 7 and Figure 10)

Exposure to whole body gamma irradiation induced a highly

significant increases (LSD Plt001) in the activities of metallothioneins

and TBARS concentrations in the liver homogenate of irradiated rats with

percentage change of 5983 and 2935 respectively While it produced

significant depletion of reduced glutathione (-2927) concentration (LSD

Plt 001) when compared with control one

Treatment with FEO caused non-significant changes in liver reduced

glutathione (GSH) levels of TBARS (LPO) and a highly significant

(LSDPlt001) increase in metallothioneins (MTs) compared to normal

control group recording percentage change of 033 563 and 4082

respectively Administration of fennel oil produced a highly significant (LSD

Plt001) increase in GSH compared to irradiated group recording

percentage change from -2927 to -1456 from control group while a

marked modulation in lipid peroxidation were observed and can minimize

the severity of changes occurred in the levels of TBARS compared with the

irradiated rats (LSD Plt001) It minimized the percentage of TBARS from

2935 to 883 However a significant decrease of MTs from 5983 to

3533 was recorded in comparison with irradiated group



Results

٧٦

Table 7 Effect of Foeniculum vulgare essential oil (FEO) on antioxidant status in liver fresh tissues of normal and irradiated rats

Parameters

Groups GSH (mgg tissue)

TBARS (nmolg)

MTs (mgg tissue)

Control 7492 plusmn 2096a 3625 plusmn 146c 27 34 plusmn 045c


5299 plusmn 087c -2927

4689 plusmn 076a 2935

437plusmn 1025a


7467 plusmn 114a

033 3829 plusmn0863bc

563 3850 plusmn 072b


6401plusmn 131b -1456

3945plusmn 099b 883

37 plusmn 077b 3533

F probability Plt0001 Plt0001 Plt0001




Fig 10 Effect of FEO on antioxidant status in liver fresh tissues of normal and irradiated rats

0

10

20

30

40

50

60

70

80

90


Groups

Con

cent

ratio

ns

GSH (mggtissue) TBARS (nmolg) MTS (mggtissue)

a

c

a

b

c

a

bc b

c

ab b

Results

٧٧

8 Effect of Foeniculum vulgare on antioxidant status in kidney fresh

tissues (Table 8 and Figure 11)

The results represented in table 8 showed that whole body gamma

irradiation at single dose (65 Gy) resulted in a highly significant increases

(LSD Plt001) in metallothioneins and TBARS concentrations in the

kidney homogenate of irradiated rats (Plt 0001) with percentage change of

6727 and 6114 respectively On the other hand a highly significant

depletion in reduced glutathione (GSH) was observed as compared to

control group (LSD Plt001) recording percentage change of -5336

Group treated with FEO showed non-significant changes in kidney

levels of reduced glutathione (GSH) TBARS (LPO) and metallothioneins

(MTs) recording percentage changes of -248 342 and -476 of the

control level

Administration of fennel oil to irradiated rats produced a highly

significant increase in kidney GSH level as compared to the irradiated

group the values returned toward normal one to be -2037 of the normal

control instead of being -5336 for irradiated group On the other hand

TBARs and metallothioneins levels were highly significantly decreased as

compared to irradiated group with a percentage change of 3277 and

879 instead of being 6114 and 6727

Concerning one-way ANOVA test it was found that the general

effect between groups was very highly significant (Plt0001) throughout the

experiment

Results

٧٨

Table 8 Effect of Foeniculum vulgare essential oil (FEO) on antioxidant status in kidney fresh tissues of normal irradiated and treated rats

Parameters Groups

GSH (mgg tissue)

TBARS (nmolg)

MTs (mggtissue)

Control 6655 plusmn 0875a 4351plusmn098c 2206 plusmn 066bc


3104 plusmn 0826c -5336

7011plusmn104a 6114

369 plusmn 102a 6727


6490plusmn 152a -248

4500 plusmn 07c 342

2101 plusmn 056c -476


5299 plusmn 095b -2037

5777plusmn041b 3277

24 plusmn 047b 879


LSD at the 5 level 313 238 207 LSD at the 1 level 423 321 279


Fig 11 Effect of FEO onantioxidant status in kidney fresh tissues of normal and irradiated rats

0

10

20

30

40

50

60

70

80


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

c

b

bc

a

c b

Results

٧٩

9 Concentration levels of Zn (microgg fresh tissue) in liver spleen kidney

and testis tissues of different rat groups (Table 9 and Figure 12)

From table (9) concerning with the concentration levels of Zn in

different tissue organs it was observed that whole body gamma irradiation

at 65 Gy induced significant elevation (LSD lt001) in Zn concentration

levels in liver and testis with percentage change of 1405 and 1089

respectively non significant increase (Pgt005) in spleen (911) and

significant decrease (Plt001) in kidney (-817) Treatment with fennel oil

induced non-significant change in zinc levels in liver (411) spleen

(1085) and testis (-475) and significant increase kidney (613) in

comparison with the control The combined treatment of irradiation and

fennel oil induced significant retention of zinc in liver (1592) spleen

(5557) and testis (1425) and non-significant changes were recorded in

kidney (-216) in comparison with control group While in comparison

with irradiated group there were significant increase in spleen and kidney

while there were non-significant increase in liver and testis

One way AVOVA test revealed that the general effect on Zn level

between groups was very highly significant (F probability Plt0001) in all

tested organ through the experiment

Results

٨٠

Table 9 Concentration levels of Zn (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

Testis Kidney Spleen Liver

Tissues Groups

3095plusmn095b3097plusmn071b 2908plusmn111b 2946plusmn 043bControl

3432plusmn056a

1089 2844plusmn06c

-817 3173plusmn145b

911 336 plusmn065a

1405 Irradiated (IRR) Ch of Control

2948plusmn063b

-475 3287plusmn056a

613 3224plusmn140 b

1085 3076plusmn 056b


3536plusmn047a 1425

303plusmn 055b -216

4524plusmn28a 5557

3415plusmn056a

1592 Irradiated(FEO) Ch of Control

Plt0001 Plt0001 Plt0001 Plt0001 F probability 196 177 498 160 LSD at the 5 level 2657 239 6715 217 LSD at the 1 level


Fig 12 Concentration levels of Zn in different tissue organs of different rat groups

0

10

20

30

40

50

60


Groups

Con

cent

ratio

n (micro

gg

tissu

e)

Liver Spleen Kidney Testis

ba

ba

bb b

a

bc b

aba

b

a

Results

٨١

10 Concentration levels of Cu (microgg fresh tissue) in liver spleen

kidney and testis tissues of different rat groups (Table 10 and Figure

13) Concerning with the concentration levels of copper displayed

significant reduction (LSD Plt001) in copper levels in liver and kidney

with percentage change of -2248 and -1661 and non-significant (LSD

Pgt005) change in spleen 974 and testis 174 in irradiated group

Treatment with fennel oil induced non-significant (LSD Pgt005) increase

in copper levels in spleen and kidney with percentage change of 308 and

982 respectively and non significant decrease in liver -749 and testis -

913 While in irradiated treated there were non-significant (LSD

Pgt005) changes in copper levels in liver 413 and testis 304

significant increase in spleen 7282 and significant decrease in kidney -

2410 in comparison with control group while in comparison with

irradiated group there were significant increase in liver and spleen and non

significant change in kidney and testis

With regards one way ANOVA the effect between groups on cu in

livers kidney and spleen was very highly significant (F-probability

Plt0001) while the effect in testis was only significant (Plt005) through

out the experiment

Results

٨٢

Table 10 Concentration levels of Cu (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

Tissues Groups

Liver

Spleen Kidney Testis

Control 387plusmn014ab 195plusmn0075b 560plusmn030a 230plusmn007a


3 plusmn 005c -2248

214plusmn 01b 974

467plusmn018b -1661

234 plusmn005a 174


358plusmn009b -749

201plusmn0085b 308

615plusmn019a 982

209 plusmn009b -913


403plusmn012a 413

337plusmn026a 7282

425plusmn011b -2410

237 plusmn011a 304

F probability Plt0001 Plt0001 Plt0001 Plt005

LSD at the 5 level 031 043 0609 024

LSD at the 1 level 042 0585 0822 0325

Values are expressed as mean plusmn SE of 8 observations Means which share the same superscript symbol(s) are not significantly different Pgtoo5 (1) If the difference between two means is higher than value of LSD at the 5 level the effect will be significant (Plt005) (2) If the difference between two means is higher than value of LSD at the 1 level the effect will be highly significant (Plt001)

Fig 13 Concentration levels of Cu in different tissue organs of different rat groups

0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


ab

cb

a

b b b

a

a

b

a

b

ab a ab

Results

٨٣

11 Concentration levels of Fe (microgg fresh tissue) in liver spleen kidney


The levels of iron were significantly increased in liver and spleen of

irradiated group with percentage changes of 1288 and 31048

respectively while it insignificantly decreased in kidney (-309) and

increased in testis (1369) respectively Fennel treatment induced more

significant (LSD Plt001) retention of iron in spleen (7319) only and

non significant change in liver (386) kidney (052) and testis (-

972) Fennel treatment with irradiation induced significant increase of

iron levels in spleen (69733) and kidney (1209) in comparison with

the control and irradiated In liver (11522) Fe concentration was

significantly increased in comparison with normal control group and was

significantly decreased when compared to irradiated group While the Fe

concentration level in testis (1024) was non-significantly affected when

compared to control and irradiated group

With regards one way ANOVA the effect on Fe between groups in

livers kidney and spleen was of (F-probability Plt0001) while the effect

in testis was only significant (Plt005) through out the experiment

Results

٨٤

Table 11 Concentration levels of Fe (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

Tissues Groups

Liver

Spleen kidney Testis

Control 8001plusmn070c 4006plusmn450d 7658plusmn130b 4178plusmn130ab


18307plusmn31a 12881

16444plusmn171b 31048

7421plusmn301b -309

475plusmn217a 1369


831plusmn073c 386

6938plusmn198c 7319

7698 plusmn092b 052

3772plusmn295b -972

Irradiated+(FEO) Ch of Control

1722plusmn39b 11522

319412plusmn10802a

69733 8584 plusmn 17a

1209 4606plusmn273a

1024 F probability Plt0001 Plt0001 Plt0001 Plt005

LSD at the 5 level 740 16108 550 690

LSD at the 1 level 994 21732 742 930


Fig 14 Concentration levels of Fe in different tissue organs of different rat groups

0

50

100

150

200

250

300

350


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)

Liver Spleen10 Kidney Testis

c

d

b

ab

ab

ba

c c b

b

b

a

a

a

Results

٨٥

12 Concentration levels of Se (ngg fresh tissue) in liver spleen kidney


The concentration levels of selenium were significantly increased

(LSD Plt001) in liver (2581) spleen (10975) and testis (2219)

while non-significantly decreased in kidney (-477) as a result of whole

body gamma irradiation Fennel oil treatment induced significant increase

in liver (8580) spleen (8260) kidney (1248) and non significant

increase in testis (1032) compared to control group The combined

treatment and irradiation induced more selenium retention in liver

(2648) spleen (24776) and testis (4549) and non significant

increase in kidney (799) in comparison with control while in comparison

with irradiated there was significant increase in spleen kidney and testis

non significant increase in liver

One way ANOVA depicted that the effect on Se between groups

was very highly significant (F-probability Plt0001) in livers spleen and

testis while it was only highly significant (Plt001) in kidney through out

the experiment

Results

٨٦

Table 12 Concentration levels of Se (ngg fresh tissue) in liver spleen

kidney and testis tissues of different rat groups

Tissues

Groups Liver


Control 1267plusmn408c 14526plusmn608d 49532plusmn169bc 4064plusmn114c

Irradiated Ch of Control

1594plusmn616b 2581

30468plusmn1230b 10975

4717plusmn1494c -477

4966plusmn2470b 2219

Treatment (FEO) Ch of Control

23542plusmn84a 85 80

26525plusmn125c 8260

55714plusmn1655a 1248

44836plusmn259bc 1032

Irradiated+ FEO Ch of Control

16025plusmn69b 26 48

50516plusmn1512a

24776 5349plusmn225 ab

799 5913plusmn275a

45 49 F probability Plt0001 Plt0001 Plt001 Plt0001

LSD at the 5 level 19047 34689 5207 6750

LSD at the 1 level 25696 468 7025 9107


Fig 15 Concentration levels of Se in different tissue organs of different rat groups

0

100

200

300

400

500

600

700


Groups

Con

cent

ratio

n (n

gg

tissu

e)


cb

a

bd

b

c

abcc

a ab

c

bbc

a

Results

٨٧

13 Concentration levels of Ca (microgg fresh tissue) in liver spleen


16)

The concentration levels of calcium were significantly increased

(LSD Plt001) in spleen (16797) kidney (3365) testis (6247) and

significant decrease in liver (-709) of irradiated rats Fennel treatment

induced significant (LSD Plt001) increase of calcium levels in spleen

(2583) kidney (4893) testis (5012) and non-significant (LSD

Pgt005) change in liver (384) in comparison with normal control group

The combined treatment of fennel oil and irradiation induced significant

increase of calcium in spleen (40784) kidney (5711) and testis

(11782) in comparison with control and irradiated groups except in liver

there was a non-significant increase (515) as compared with control

group and a significant increase compared with irradiated one

With regard one-way ANOVA it was found that the effect on

calcium between groups was very highly significant (F-probability

Plt0001) in spleen kidney and testis while it was only highly significant

(Plt001) in liver through out the experiment

Results

٨٨

Table 13 Concentration levels of Ca (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

Tissues Groups

Liver

spleen kidney Testis

Control 6296plusmn079a 7971plusmn099d 8440plusmn145d 4770plusmn081d


5849plusmn166b -709

2136plusmn127b 16797

1128plusmn096c

3365 775plusmn071b


6538plusmn133a 384

1003plusmn081c 2583

1257plusmn131b 4893

7161plusmn102c


662plusmn15a 515

404plusmn111a 40784

1326plusmn092a 5711

1039plusmn064a


LSD at the 5 level 394 306 329 230

LSD at the 1 level 5324 413 443 311


Fig 16Concentration levels of Ca in different tissue organs of differnent rat groups

0

50

100

150

200

250

300

350

400

450


Groups

Con

cent

artio

n (micro

gg

tiss

ue)


a b a ad

b

c

a

dc b a

db c

a

Results

٨٩

14 Concentration levels of Mg (microgg fresh tissue) in liver spleen


17)

The levels of magnesium were insignificantly (LSD Pgt005)

increased in liver (644) and testis (897) of irradiated group while it

significantly (Plt005) and insignificantly (Pgt005) decreased in spleen (-

1812) and kidney (-158) respectively In fennel oil treated group

there were significant increases in liver (1589) and non-significant

changes in kidney (171) spleen (686) and testis (-308) The

combined treatment of fennel and irradiation induced more magnesium

retention in liver (1401) spleen (3366) and kidney (574) while non

significant increase in testis (1003) when compared with control group

while in comparison with irradiated group there were significant increase in

spleen and kidney and non significant increase in liver and testis

With regard one-way ANOVA it was found that the effect on Mg

between groups was very highly significant (F-prob Plt0001) in spleen

highly significant in liver (LSD P001) and significant (LSD Plt005) in

kidney and testis

Results

٩٠

Table 14 Concentration levels of Mg (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

Tissues Groups

Liver


Control 41814plusmn123c 50035plusmn149b 42086plusmn594b 3424plusmn594a b


44505plusmn108bc 644

4097plusmn1488c

-1812 41419plusmn49b

-158 3731plusmn1314a

897 Treated(FEO) Ch of Control

4846plusmn107a 15 89

53465plusmn196b 686

42807plusmn663ab

171 33184plusmn901b

-308 Irradiated + FEO Ch of Control

4771plusmn168b 1410

66878plusmn369a 3366

445012plusmn84a 574

37674plusmn1703a


LSD at the 5 level 3737 6783 1908 3485

LSD at the 1 level 5041 9151 2575 4702


Fig 17 Concentration levels of Mg in different tissue organs of differnent rat groups

0

100

200

300

400

500

600

700

800


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


c bca ab

b

c

b

a

b b ab a

aba

ba

Results

٩١

15 Concentrations of Mn (microgg fresh tissue) in liver tissue of different

rat groups (Table 15 and Figure 18)

The results revealed that irradiated group exhibited significant

(LSD Plt001) decrease in manganese in liver (-1353) organ In fennel

oil group there was non-significant change (Pgt005) in liver (-075)

manganese while in combined treatment of fennel and irradiation there

was non-significant change in Mn level in liver when compared with

control group with percentage change of (075) while in comparison

with irradiated group there were significant increase (LSD Plt005) of Mn

in liver The samples of the other organs (kidney spleen as well as testis

were below to the detection limit with flame technique)

One way ANOVA revealed that the effect between groups on the

liver Mn was significant (F-probability Plt005) throughout the

experiment

Results

٩٢

Table 15 Concentration levels of Mn (microgg fresh tissue) in liver spleen kidney and testis tissues of different rat groups

Tissues Groups

Liver

Control 133plusmn0064a


115plusmn0046b -1353

Treatment (fennel oil) Ch of Control

132plusmn0065a -075

Irradiated + fennel oil Ch of Control

134 plusmn 0021a 075

F probability Plt005



Values are expressed as mean plusmn SE of 8 observations Means which share the same superscript symbol(s) are not significantly different Pgt005 (1) If the difference between two means is higher than value of LSD at the 5 level the effect will be significant (Plt005) (2) If the difference between two means is higher than value of LSD at the 1 level the effect will be highly significant (Plt001) The samples of kidney spleen as well as testis were below to the detection limit

Fig 18 Concentration levels of Mn in different tissue organs of difffernt rat groups

0

02

04

06

08

1

12

14

16


Groups

Con

cnet

ratio

n (micro

gg

tiss

ue)

Liver

a

b

a a

Results

٩٣

16 Concentration levels of metals in fennel plants (microgg) for all metals

except Se (ngg)

Table (16) showed the highly content of metal in crude Foeniculum

vulgare plants

Table 16 Concentration levels of metal in fennel plants (microgg) for all

metals except Se (ng g) dry wt

ConcentrationElementConcentration

Element

40734 plusmn 8391 Ca12877plusmn 124Fe (15137 plusmn 094)X 102Mg1214plusmn 008Cu

6957 plusmn 728Se325 plusmn 099Zn 653 plusmn 233Mn

Each value represents the mean of 8 samples recorded plusmn SE

Discussion

٩٤

Ionizing radiations are known to induce oxidative stress through the

generation of reactive oxygen species resulting in an imbalance in the pro-

oxidant antioxidant status in the cells (Bhosle et al 2005) Multiple

processes may lead to cellular damage under irradiation but the generation

of oxygen free radicals following by lipid peroxidation may be one of the

key components in this cascade of events (Soloviev et al 2002) Radiation

generates reactive oxygen species (ROS) that interact with cellular

molecules including DNA lipids and proteins (Tominaga et al 2004)

Results of the present study indicates that exposure of rats to whole

body gamma irradiation at single dose (65 Gy) lead to biochemical

disorders manifested by elevation of transaminase (AST) and alkaline

phosphatase (ALP) bilirubin lipids (Cholesterol and Triglycerides) urea

creatinine and lipid peroxidation (LPO) as well as metallothioneins (MTs)

while a sharp decrease in glutathione contents total protein albumin and

testosterone hormone was recorded in addition to some changes in essential

trace elements (Fe Zn Cu Ca Mg and Se) in the tissues of studied organs

(liver spleen kidney and testis)

61 Biological Effects of Ionizing Radiation

611 Effects of γ-irradiation on liver functions The rise in the serum transaminases activities and alkaline

phosphatase in irradiated animals may be due to the drastic physiological

effect caused by irradiation either directly by interaction of cellular

membranes with gamma ray or through the action of free radicals produced

by radiation Liver damage may increase the cell membrane permeability

accompanied with rise in the transaminases activities Accordingly the

Discussion

٩٥

observed increase in serum transaminase activities and ALP is expected as

a consequence for the increase in activities of the liver enzymes These

findings are supported by previous finding reported by Roushdy et al

(1984) Kafafy (2000) Ramadan et al (2001) and Nada (2008) who

explained that changes in the enzymatic activities after irradiation may be

due either to the release of enzymes from radiosensitive tissues or to

changes in its synthesis and may be related to the extensive breakdown of

liver parenchyma and renal tubules

Khamis and Roushdy (1991) explained that the increase in serum

aminotransferase activities by radiation may be due to the damage of

cellular membranes of hepatocytes which in turn leads to an increase in the

permeability of cell membranes and facilitates the passage of cytoplasmic

enzymes outside the cells leading to the increase in the aminotransferase

activities in blood serum Also ionizing radiation enhanced lipid

peroxidation in cell membrane which contains fatty acids and excessive

production of free radicals this in turn increases the cytoplasmic

membrane permeability to organic substances and causes leakage of

cystosolic enzymes such as AST ALT (Weiss and Lander 2003)

The clinical and diagnostic values associated with changes in blood

enzymes concentrations such as AST ALT ALP and bilirubin have long

been recognized (Martin and Freidman 1998) Increased levels of these

diagnostic markers of hepatic function in irradiated rats are implicative of

the degree of hepatocellular dysfunction caused by the radiation The

increase in the levels of serum bilirubin reflected the depth of jaundice and

the increase in transaminases was the clear indication of cellular leakage

and loss of functional integrity of the cell membrane (Saraswat et al

1993)

Discussion

٩٦

Omran et al (2009) revealed that significant elevation in AST

ALT ALP and bilirubin were recorded post exposed to gamma-irradiation

which reflects detectable changes in liver functions Such elevation was in

agreement with (Hassan et al 1996) They reported that this elevation

directly by interaction of cellular membranes with gamma-rays or through

an action of free radicals produced by this radiation

In the present study the marked elevation in the levels of ALT AST

and ALP might be due to the release of these enzymes from the cytoplasm

into the blood circulation rapidly after rupture of the plasma membrane and

cellular damage Elevated liver marker enzymes in serum are a reflection of

radical-mediated lipid peroxidation of liver cell membrane Several

investigations indicated that exposure to radiation increases free radicals

activity The generation of free radicals is considered to be the primary

cause of the damaging effect These free radicals combined with the

cellular lipid and proteins which in turn initiate lipid peroxidation process

and protein carbonylation resulting in structural changes of bio-membranes

and loss of liver integrity and decreased metabolic activity (Guumlven et al

2003)

El-Kafif et al (2003) explained that this increase may be ascribed

to the irradiation-induced damage to hepatic parenchymal cells as well as

extra hepatic tissues with a subsequent release of the enzymes into the

blood stream It may also be attributed to the structural damage in spleen

lymphnodes mature lymphocytes (Albaum 1960) Moreover the

destruction of erythrocytes due to ionizing radiation and the release of their

enzymes can not be excluded as a causative factor for the rise in these

enzymes (Azab et al 2001) The increased activity of serum ALP by

gamma-irradiation agrees with Tabachnick et al (1967) who attributed it

Discussion

٩٧

to the enzyme release from the tissues to the blood stream or to liver

disturbances particularly due to defects in cell membrane permeability (El-

Missiry et al 1998)

The variation in transaminases activities may be due to certain

damage in some tissue like heart liver kidney and skeletal muscles Fahim

et al (1993) mentioned that whole body gamma-irradiation of rats showed

significant changes in the activities of transaminases which are dependent

on the time lapses after irradiation and the type of tissue containing the

enzyme These results may be attributed to the state of hypoxia of

parenchyma for contracting fibrous tissue and the increased permeability of

hepatic cell membrane due to irradiation exposure with release of ALT

enzyme to circulation The increased serum level of ALT in rats is a sign of

liver parenchymal cell destruction induced by whole body gamma

irradiation We hypothesized that the elevation in serum level of ALT

activity observed in the present study may reflect hypotonic potency of

sub-chronic exposure effect of gamma ray on liver This effect could be an

essential process for the liver to restore the balance of different free amino

acids that might have been disturbed through out recovering mechanisms

612 Effect of gamma radiation on protein profile

Serum proteins are synthesized and secreted by several cell types

depending on the nature of the individual serum protein An important

function of serum protein is the maintenance of the normal distribution of

body water by controlling the osmotic balance between the circulating

blood and the membrane of tissues and the transport of lipids hormones

and inorganic materials (Harper et al 1977) The results obtained in this

work showed that there is significant decrease in serum total proteins and

albumin and non-significant effect for globulin and albuminglobulin ratio

Discussion

٩٨

Saada (1982) Roushdy et al (1984) Srinivasan et al (1985) and

Haggag et al (2008) suggested that the decrease in serum protein in

irradiated rats might be the result of damage of vital biological processes or

due to changes in the permeability of liver kidney and other tissues

resulting in leakage of protein especially albumin via the kidney

The decrease in blood total protein might be due to the slow rate in

synthesis of all protein fractions after irradiation (Reuter et al 1967

Takhtayev and Tadzh 1972) This decrease coincides with the decrease in

serum t-protein reported by other workers in irradiated rats which may be

due to radiation damage to the liver (Kafafy and Ashry 2001) Roushdy

et al (1989) Samarth et al (2001) and El-Kafif et al (2003) suggested

that the decrease in protein in irradiated rats might be the result of

eitherdamage of biological membranes or to changes in the permeability of

the liver

Several investigations indicated that exposure to radiation increases

free radical activity The generation of free radicals is considered to be the

primary cause of damaging effects Radiation induced lipid peroxidation

reduce protein synthesis and cause disturbances in the enzyme activity of

the liver (Kadiiska et al 2000)

Albumin is the most abundant circulatory protein and its synthesis is

atypical function of normal liver cells Low levels of albumin have been

reported in the serum of patients and animals with hepatocellular cancer

(Gray and Meguid 1990) The fall in albumin levels could probably

contribute to the damage in the liver cells induced by irradiation

In the present study there were a decrease in contents of total

proteins albumin and total globulins in serum of rats irradiated with

Discussion

٩٩

gamma-irradiation indicating liver injury (El-Missiry et al 2007 Ali et

al 2007) These results are in accordance with other studies (Bhatia and

Manda 2004) using high-energy radiation from cobalt source Therefore

it is suggested that oxidative stress as a result of gamma-irradiation is

linked to the organ damage following exposure to ionizing radiation

Kempner (2001) explained that this decrease in proteins level may be due

to gamma-irradiation can damage or inactivate proteins by two different

mechanisms First it can rupture the covalent bonds in target protein

molecules as a direct result of a photon depositing energy into the

molecule Second it can act indirectly link with a water molecule

producing free radicals and other non-radical reactive oxygen species that

are in turn responsible for most (999) of the protein damage

613 Effects of γ-irradiation on renal functions In the present study plasma urea and creatinine levels which are

considered as a markers of kidneys function were significantly elevated

after exposure the animals to γ- irradiation indicating renal impairment

(Altman et al 1970 Hassan et al 1994 Mahmoud 1996 Ramadan et

al 1998) The increase in blood creatinine and urea has been reported after

exposure to irradiation and secondary to renal damage (Roushdy et al

1985 Abdel-Salam et al 1990) In addition the elevation in urea may be

attributed to an increase in nitrogen retention or excessive protein

breakdown (Varley et al 1980)

Mahdy (1979) attributed the increase in urea and creatinine

concentrations after exposure of rats to γ-radiation to associated interaction

of irradiation with their sites of biosynthesis The significant increment in

the concentration of serum urea in rats by gamma-irradiation could be due

to the result of radiation-induced changes in amino acids metabolism The

Discussion

١٠٠

elevation of proteins catabolic rate observed in irradiated rats is

accompanied by a decrease in liver total proteins and an increase in the

content of non-protein nitrogen of both liver and serum as well as increases

levels of serum amino acids and ammonia (El-Kashef and Saada 1985)

that depends mainly on the protein destruction after irradiation The

impaired detoxification function of liver by irradiation could also

contribute to the increase of urea in the blood (Robbins et al 2001) or

deteriorating renal performance (Geraci et al 1990) Serum creatinine

elevation by irradiation was attributed by El-Kashef and Saada (1988) to

its interaction with the creatinine sites of biosynthesis

The present results are in accordance with Abou-Safi and Ashry

(2004) who suggested that the significant increase in serum urea was

attributed to the increase in glutamate dehydrogenase enzyme levels which

might increase carbamyl phosphate synthetase activity leading to an

increase in urea concentration Also Ramadan et al (2001) and Kafafy

(2004) concluded that the increase in urea could be an indication for the

elevation of protein catabolic rate

614 Effect of γ-irradiation on lipid metabolism Free radical impairs liver functions and can be a major reason of

hormonal imbalance This imbalance induces hyperlipidemia through its

multiple effects on lipid metabolism including increased synthesis of

cholesterol triglyceride (Bowden et al 1989) In the present study

marked significant elevation was observed in lipid (cholesterol

triglyceride) in irradiated rats Our results are in agreement with those of

Markevich and Kolomiitseva (1994) Zahran et al (2003) Abbady et al

(2004) Kafafy et al (2005b) Said and Azab (2006) and Nada (2008)

who reported an increase of lipids in plasma level of rats post irradiation

Discussion

١٠١

They attributed the hypercholesterolemia conditions to the stimulation of

cholesterol synthesis in the liver after gamma-irradiation Moreover Bok et

al (1999) contributed the irradiation-induced hypercholesterolemia to the

increase of activation of HMG-CoA reductase enzyme the key regulatory

enzyme in the reduction of the overall process of cholesterol synthesis

Sedlakova et al (1986) explained that the increase in serum

triglyceride level after irradiation might result from inhibition of

lipoprotein lipase activity leading to reduction in uptake of

triacylglycerols Mahmoud (1996) attributed the hyperlipidemic state

under the effect of gamma-irradiation to the stimulation of liver enzymes

responsible for the biosynthesis of fatty acids by gamma radiation and

mobilization of fats from adipose tissue to blood stream

The increase in cholesterol and triglycerides levels after exposure to

irradiation compared to control confirms previous reports which revealed

that whole body exposure to gamma radiation induces hyperlipidemia (El-

Kafif et al 2003 Feurgard et al 1998) They reported that increased

level of serum cholesterol fractions was probably due to its release from

tissues destruction of cell membranes and increase rate of cholesterol

biosynthesis in the liver and other tissues The hyperlipidemic state

observed after irradiation could be attributed to the mobilization of fats

from the adipose tissues to the blood stream (Chajek-Shaul et al 1989) in

addition to mitochondrial dysfunction (Madamanchi and Runge 2007)

Chrysohoou et al (2004) observed that total serum phospholipids

their fractions and cholesterol were significantly changed after radiation

exposure Furthermore some serum lipid polyunsaturated fatty acids were

significantly altered since these alterations are a sign of lipid peroxidation

(Feugard et al 1998)

Discussion

١٠٢

615 Effect of γ-irradiation on serum testosterone Radiation is one of the cytotoxicants that can kill testicular germ

cells and so produce sterility Selective destruction of the differentiating

spermatogonia at low doses of irradiation [2ndash6 gray (Gy)] is a general

phenomenon observed in rodents and humans resulting in a temporary

absence of spermatogenic cells (Oakberg 1959 Clifton and Bremner

1983) However the stem spermatogonia are relatively radioresistant they

immediately repopulate the seminiferous epithelium as indicated in mice

(Oakberg 1959) In this study a marked significant decrease in serum testosterone

was observed in irradiated rats This result is in agreement with those of El-

Dawy and Ali (2004) and SivaKumar et al (2006) who reported a

decrease in testosterone in serum of irradiated rats

The testis consists of semineferous tubules which form the sperm

and the interstitial leydig cells which secret testosterone The function of

the testis is controlled by the hypothalamic pituitary mechanism In the

present study the disturbed testosterone level might be attributed to

hypothalamic and pituitary gland dysfunction which interferes with

hormone production The decrease in male sex hormone (testosterone)

might also be attributed to the production of free radicals and increase of

LPO in testis tissue which attack the testicular parenchyma causing damage

to the semineferous tubules and leydig cells (Constine et al 1993)

Testosterone secretion is regulated by pituitary LH hormone FSH

may also augment testosterone secretion by inducing maturation of the

leydig cells Testosterone also regulates the sensitivity of the pituitary

gland to hypothalamic releasing factor leuteinizing hormone-releasing

hormone (LHRH) Although the pituitary can convert testosterone to

Discussion

١٠٣

dihydrotestosterone and to estrogens testosterone itself is the primary

regulation of gonadotrophins secretion (Griffin and Wilson 1987)

Testicular exposure to ionizing radiation in animals induced significant

changes in serum gonadotrophins and semen parameters The present data

revealed that irradiation induced decrease in testosterone level This may be

due to impairment in leydig cell function In addition Liu et al (2005)

referred these changes to the influence on cell steroidogenesis resulting in

reduction of testosterone

616 Effect of γ-irradiation on antioxidant status

6161 Lipid peroxidation The present data revealed significant acceleration in the oxidation of

lipid associated with depletion in GSH content The significant

acceleration in lipid peroxidation measured as thiobarbituric acid reactive

substances (TBARS) content is attributed to the peroxidation of the

membrane unsaturated fatty acids due to free radical propagation

concomitant with the inhibition in bio-oxidase activities (Zheng et al

1996) Moreover Chen et al (1997) attributed the increase in lipid

peroxidation level after irradiation to inhibition of antioxidant enzymes

activities Ionizing radiations produced peroxidation of lipids leading to

structural and functional damage to cellular membranous molecules

directly by transferring energy or indirectly by generation of oxygen

derived free radical (OH) superoxide (O2-) and nitric oxide (NO) are the

predominant cellular free radicals (Spitz et al 2004 Joshi et al 2007)

The polyunsaturated fatty acids present in the membranes

phospholipids are particularly sensitive to attack by hydroxyl radicals and

other oxidants In addition to damaging cells by destroying membranes

lipid peroxidation (LPO) can result in the formation of reactive products

Discussion

١٠٤

that themselves can react with and damage proteins and DNA (Lakshmi et

al 2005) Oxidative stress leads to over production of NO which readily

reacts with superoxide to form peroxynitrite (ONOO-) and peroxynitrous

acid which they can initiate lipid peroxidation (Millar 2004)

MDA secondary product of lipid peroxidation is used as an

indicator of tissue damage (Zhou et al 2006) Radiation exposure has

been reported to be associated with increased disruption of membrane

lipids leading to subsequent formation of peroxide radicals (Rajapakse et

al 2007)

6162 Glutathione The present results revealed significant depletion in glutathione after

radiation exposure which might be resulted from diffusion through

impaired cellular membranes andor inhibition of GSH synthesis

Pulpanova et al (1982) and Said et al (2005) explained the depletion in

glutathione (GSH) content by irradiation by the diminished activity of

glutathione reductase and to the deficiency of NADPH which is necessary

to change oxidized glutathione to its reduced form These data confirms the

previous reports of Osman (1996) El-Ghazaly and Ramadan (1996) and

Ramadan et al (2001)

The depletion in glutathione and increase in MDA are in agreement

with those recorded by Bhatia and Jain (2004) Koc et al (2003) and

Samarth and Kumar (2003) who reported a significant depletion in the

antioxidant system accompanied by enhancement of lipid peroxides after

whole body gammandashirradiation Under normal conditions the inherent

defense system including glutathione and the antioxidant enzymes

protects against oxidative damage Excessive liver damage and oxidative

stress caused by γ-irradiation might be responsible for the depletion of

Discussion

١٠٥

GSH Oxidative stress induced by γ-irradiation resulted in an increased

utilization of GSH and subsequently a decreased level of GSH was

observed in the liver tissues Depletion of GSH in vitro and in vivo is

known to cause an inhibition of the glutathione peroxidase activity and has

been shown to increase lipid peroxidation (Jagetia and Reddy 2005)

The decrease in reduced glutathione by irradiation could be due to

oxidation of sulphhydryl group of GSH as a result decrease in glutathione

reductase the enzyme which reduces the oxidized glutathione (GSSG) into

a reduced form using NADPH as a source of reducing equivalent (Fohl

and Gunzler 1976) GSH can function as antioxidant in many ways It can

react chemically with singlet oxygen superoxide and hydroxyl radicals and

therefore function directly as free radical scavenger GSH may stabilize

membrane structure by removing acyl-peroxides formed by lipid

peroxidation reactions (Price et al 1990)

Dahm et al (1991) attributed the decrease in liver GSH content to

the inhibition of GSH efflux across hepatocytes membranes Moreover

reduced glutathione has been reported to form either nucleophil-forming

conjugates with the active metabolites or act as a reductant for peroxides

and free radicals (Moldeus and Quanguan 1987) which might explain its

depletion The resultant reduction in GSH level may thus increase

susceptibility of the tissue to oxidative damage including lipid

peroxidation

Interaction of radiation with biological molecules produced toxic

free radicals leading to structural and functional damage to cellular

membranes Consequently a dramatic fall in glutathione and antioxidant

enzymes leading to membrane lipid peroxidation and loss of protein thiols

(Devi and Ganasoundari 1999) Irradiation has been reported to cause

Discussion

١٠٦

renal GSH depletion and lipid peroxides accumulation in different organs

(Siems et al 1990 El-Habit et al 2000 Yanardag et al 2001) It was

found that the level of elevation in lipid peroxidation after irradiation is in

proportion to radiation dose and elapsed time (Ueda et al 1993)

Moreover the formation of lipid peroxidation ultimately would alter the

composition of the glumerular basement membrane (Haas et al 1999)

Earlier investigations by Kergonou et al (1981) and Ronai and Benko

(1984) showed elevation in the MDA of different organs including kidney

of rats exposed to whole body gamma irradiation the former hypothesized

that MDA is released from tissues in plasma and trapped from plasma in

kidney while the later reported that the increase of MDA level is a dose

related manner with characteristic time dynamics

Bump and Brown (1990) reported that GSH is a versatile protector

and executes its radioprotective function through free-radical scavenging

restoration of the damaged molecules by hydrogen donation reduction of

peroxides and maintenance of protein thiols in the reduced state Further

lower depletion of blood and liver GSH levels in irradiated animals might

have been due to higher GSH availability which enhanced the capability of

cells to cope with the free radicals generated by radiation

6163 Metallothioneins Results also indicate that metallothioneins (MTs) were increased

after treatment with gamma-irradiation These data are in agreement with

those reported by Shiraishi et al (1986) Koropatnick et al (1989) and

Nada and Azab (2005) who stated that the induction of metallothioneins

by irradiation appears to be due to an increased synthesis of their MTs The

mechanisms of metallothionein induction by irradiation are unknown

However MTs synthesis can be induced by physical and chemical

Discussion

١٠٧

oxidative stress including free radical generators Cell killing by irradiation

is caused by unrepaired or misrepaired DNA double strand breakage Much

of the damage to DNA induced by ionizing radiation is considered to be

caused by the hydroxyl radicals produced by the radiolysis of water in cell

Thus MTs synthesis may be induced directly or indirectly by free radical

produced from irradiation (Sato and Bremner 1993)

Metallothioneins are a family of low molecular-weight cystein-rich

metal-binding proteins that occur in animals as well as in plants and

eukaryotic microorganisms Their synthesis can be induced by a wide

variety of metal ion including cadmium copper mercury cobalt and zinc

This had led to their frequent use as biomarker to show the high levels of

metals in the body MTs are involved in limiting cell injury (Sanders

1990)

Metallothioneins are also involved in protection of tissues against

various forms of oxidative stress (Kondoh and Sato 2002) Induction of

metallothioneins biosynthesis is involved in a protective mechanism

against radiation injuries (Azab et al 2004) The accumulation of certain

metals in the organs could be attributed to the disturbance in mineral

metabolism after radiation exposure (Kotb et al 1990)

Production of free radicals will not only lead to increased lipid

peroxidation but also to an induction of metallothioineins (Kaumlgi and

Schaumlffer 1988) especially in liver and kidney which will bond Zn

Alternatively the increased Zn content in these tissues might be caused by

an increased liberation of interleukin (Weglicki et al 1992) which will

lead to induction of MTs (Kaumlgi and Schaumlffer 1988) Additionally the

increased Fe content in liver may have induced the synthesis of

metallothioneins which in turn bound Zn (Fleet et al 1990)

Discussion

١٠٨


can not be replaced effectively by chemically similar elements In general

the major biological function of MTs is the detoxification of potentially

toxic heavy metal ions and regulation of the homeostasis of essential trace

metals (Ono et al 1998) In accordance with previous studies (Gerber

and Altman 1970 Shirashi et al 1986) gamma-irradiation led to a

marked elevation in zinc of liver tissues The increase may be due to

accumulation of zinc from the damage of the lymphoid organs (thymus

spleen and lymph nodes) bone marrow and spermatogonia that are

extremely radiosensitive (Okada 1970)

The radio-protective effect of Zn is known to result from its

inhibiting effect on the production of intracellular hydroxyl free radicals

mediated by redox-active metal ions (eg Cu and iron) by competiting for

the binding sites of those metal ions (Chevion 1991) The protective effect

of MTs against irradiation-induced oxidative stress was proved by several

studies (Sato et al 1989 Sato and Bremner 1993 Shibuya et al 1997)

617 Effect of γ-irradiation on trace element metabolism

6171 Zinc The protective effects of zinc against radiation hazards have been

reported in many investigations (Markant and pallauf 1996 Morcillo et

al 2000) Concerning the concentration levels of zinc in different tissue

organs we can observe that irradiation induced increases in zinc in liver

spleen and testis Similar observations were obtained by many investigators

(Yukawa et al 1980 Smythe et al 1982) they found that whole body

gamma-irradiation induced an elevation of zinc in different organs Heggen

et al (1958) recorded that the most striking changes in irradiated rats were

found in spleen where iron and zinc were increased in concentration

Discussion

١٠٩

shortly after irradiation Okada (1970) recognized that lymphoid organs as

spleen lymph nodes and bone marrow are extremely radiosensitive He

explained that zinc derived from these tissues that were damaged by

irradiation could be accumulated in liver or kidney thus stimulating the

induction of metallothioneins Sasser et al (1971) reported that the injury

produced by the radiation was probably responsible for the increased

uptake of zinc by erythrocytes The injury may have caused a shift of

plasma proteins affecting the availability of zinc to the erythrocytes or

caused erythrocytes to have an altered affinity for zinc

The antioxidant role of zinc could be related to its ability to induce

metallothioneins (MTs) (Winum et al 2007) There is increasing

evidence that MTs can reduce toxic effects of several types of free radical

including superoxide hydroxyl and peroxyl radicals (Pierrel et al 2007)

For instance the protective action of pre-induction of MTs against lipid

peroxidation induced by various oxidative stresses has been documented

extensively (Morcillo et al 2000 McCall et al 2000)

Zinc is known to have several biological actions It protects various

membrane systems from peroxidation damages induced by irradiation

(Shiriashi et al 1983 Matsubara et al 1987a) and stabilizes the

membrane perturbation (Markant and Palluaf 1996 Micheletti et al

2001 Morcillo et al 2000) Nada and Azab (2005) found that radiation

induced lipid peroxidation and elevation of metallothioneins

Metallothioneins (MTs) are involved in the regulation of zinc metabolism

and since radiation exposure produce lipid peroxidation and increases in

MTs synthesis we hyposized that the redistribution of zinc after irradiation

may be a biological protection behavior against irradiation these may

include DNA repair protein synthesis and scavenging the toxic free

Discussion

١١٠

radicals Accordingly it was suggested that an increase in zinc-iron ratio in

some organs may confer protection from iron catalyzed free radicals-

induced damage as early explained by Sorenson (1989) As essential

metals both zinc and copper are required for many important cellular

functions Zn and Cu may stimulate the SOD (Cu-Zn) activity and reduced

the damage induced by free radicals generated from ionizing radiation

(Floersheim and Floersheim 1986)

Matsubara et al (1987a) demonstrated a protective effect of zinc

against lethal damaged in irradiated mice They also found that increased

rates of zinc turnover in tissue organs in which elevated synthesis of MTs

was confirmed They assumed that MTs can work as the alternative of

glutathione when cells are in need of glutathione they speculated that zinc-

copper-thionein has a function almost equivalent to that of glutathione and

seems to be a sort of energy protein which has a protective role against

radiation stress Since radiation induced depression in glutathione

(Noaman and Gharib 2005 Nada and Azab 2005) the present results

suggested the possibility that redistribution and acceleration of zinc

metabolism have stimulated the defense mechanism against radiation

damage

6172 Copper In the present study there is a depression in the copper levels in liver

and kidney while non-significant changes in spleen and testis were

recorded in the tissue of irradiated animals Similar observations were

obtained by many investigators (Yukawa et al 1980 Smythe et al 1982

Kotb et al 1990 Nada et al 2008) who recorded that irradiation induced

decrease in copper in liver and kidney while Heggen et al (1958)

indicated that copper was increased in the spleen Cuproenzymes are able

Discussion

١١١

to reduce oxygen to water or to hydrogen peroxide Cuproenzymes posses

high affinity for oxygen depending on the number of incorporated copper

atoms (Abdel-Mageed and Oehme 1990b) these may explain the

decreases in copper due to excess utilization of cuproenzymes after

irradiation or may be due to de novo synthesis of Cu-SODs and catalase

which prevent the formation of O2 and hydroxyl radical associated with

irradiation (Fee and Valentine 1977) A significant inverse correlation

between hepatic iron and copper concentration has been demonstrated in

rats (Underwood 1977) In the present study the copper depression may

enhance the retention of iron in many organs Both absence and excess of

essential trace elements may produce undesirable effects (Takacs and

Tatar 1987)

Copper is absorbed into the intestine and transported by albumin to

the liver Copper is carried mostly in the blood stream on a plasma protein

called ceruplasmin Hepatic copper overloads to progressive liver injury

and eventually cirrhosis (Dashti et al 1992)

6173 Iron

Concerning with concentration level of iron in liver spleen kidney and

testis of different groups we observed that irradiation of animals with a

dose (65 Gy) induced significant increase of iron in liver and spleen while

in kidney and testis there were non significant changes These results are in

full agreement with those of Ludewig and Chanutin (1951) Olson et al

(1960) Beregovskaia et al (1982) and Nada et al (2008) who reported

an increase of iron in liver spleen and other tissues organ after whole body

gamma irradiation While in the kidney the changes in the iron contents

were comparatively small According to Hampton and Mayerson (1950)

the kidney is capable of forming ferritin from iron released from

Discussion

١١٢

hemoglobin It is probable that iron which presented in the kidney for

excretion and conversion to ferritin Trace elements are either integral parts

of enzyme molecules or act as acceleration or inhibitors of enzymatic

reaction (Underwood 1977) It was concluded by Noaman and Gharib

(2005) that irradiation 65 Gy induced changes in haematological

parameters and reduction of blood cell counts hemoglobin concentrations

and hematocrit values these may explain the changes in iron level in

different tissue organs Also enzymatic catalysis is the major rational

explanation of how a trace of some substances can produce profound

biological effects The studied elements in the present investigation have

already been shown to be essential for a number of biological effects and it

seems probable that gamma-irradiation interferes with some of these vital

organs The increase in value of iron may be related to the inability of bone

marrow to utilize the iron available in the diet and released from destroyed

red cells while the decrease in iron in other tissue organs in other

experiments may corresponds to the time of recovery of erythrocyte

function as early explained by Ludewing and Chanutin (1951) In

addition Kotb et al (1990) suggested that the accumulation of iron in the

spleen may result from disturbance in the biological functions of red blood

cells including possible intravascular hemolysis and subsequent storage of

iron in the spleen El-Nimr and Abdel-Rahim (1998) revealed the

significant change in the concentrations of essential trace elements in the

studied organs to the long term disturbances of enzymatics function and

possible retardation of cellular activity

Increased iron level may be due to oxidative stress inducing

proteolytic modification of ferritin (Garcia-Fernandez et al 2005) and

transferrin (Trinder et al 2000) Iron overload is associated with liver

damage characterized by massive iron deposition in hepatic parenchymal

Discussion

١١٣

cells leading to fibrosis and eventually to hepatic cirrohsis Accumulation

of iron-induced hepatotoxicity might be attributed to its role in enhancing

lipid peroxidation (Pulla Reddy and Lokesh 1996) Free iron facilitates

the decomposition of lipid hydroperoxides resulting in lipid peroxidation

and induces the generation of middotOH radicals and also accelerates the non-

enzymatic oxidation of glutathione to form O2- radicals (Rosser and

Gores 1995)

6174 Selenium The results of the present study showed significant increase of

selenium level in liver spleen and testis of irradiated group and a non-

significant decrease in kidney was recorded The increases of Se in liver

may attributed to the re-synthesis of glutathione (de novo synthesis)

Yukawa et al (1980) and Smythe et al (1982) recorded a decrease in Se

concentration after irradiation at doses of 4 55 and 6 Gy The decrease of

selenium might indirectly contributed to the decrease of GSH content and

its related antioxidant enzymes namely glutathione peroxidase (Pigeolet et

al 1990) This idea might be supported by the well known fact that Se is

present in the active site of the antioxidant enzyme GSH-px (Rotruck et

al 1973) and that Se deficiency decreased GSH-px in response to radiation

treatments (Savoureacute et al 1996) It has been reported that selenium plays

important roles in the enhancement of antioxidant defense system (Weiss et

al 1990 Noaman et al 2002) increases resistance against ionizing

radiation as well as fungal and viral infections (Knizhnikov et al 1991)

exerted marked amelioration in the biochemical disorders (lipids

cholesterol triglycerides glutathione peroxidase superoxide dismutase

catalase T3 and T4) induced by free radicals produced by ionizing

radiation (El-Masry and Saad 2005) enhances the radioprotective effects

and reduces the lethal toxicity of WR 2721 (Weiss et al 1987) protects

Discussion

١١٤

DNA breakage (Sandstorm et al 1989) and protect kidney tissue from

radiation damage (Stevens et al 1989) Also selenium plays important role

in the prevention of cancer and tumors induced by ionizing radiation (La

Ruche and Cesarini 1991 Leccia et al 1993 Borek 1993)

6175 Calcium and Magnesium

Calcium and magnesium are mainly existed as free ionized fractions

and as protein ligands Since magnesium is clearly associated with calcium

both in its functional role and the homeostatic mechanisms chemical and

physiological properties of calcium and magnesium show similarities

which have led to the correlations between the two divalent cations in

human and other animals (Brown 1986) The results of the present study

showed non-significant increase in level of magnesium in liver and testis of

irradiated group while it recorded a decrease in spleen and kidney

Concerning the concentration level of calcium the results clearly indicate

that calcium was significantly increased in spleen kidney and testis

Yukawa et al (1980) and Smythe et al (1982) recorded increase in Ca

and Mg after irradiation Sarker et al (1882) recorded that lethal irradiated

dose increased plasma calcium while Kotb et al (1990) observed

reduction in Ca and Mg in spleen heart and kidney Lengemann and

Comar (1961) indicated that whole body gamma irradiation has been

shown to induce changes in calcium metabolism with increase in passive

calcium transport which possibly was due to a decrease in intestinal

propulsive motility Lowery and Bell (1964) observed a rapid

disappearance of Ca45 from blood after whole body irradiation They

concluded that the maintenance of calcium homeostasis with either

parathyroid hormone or calcium salts has been observed to diminish

radiation induced lethality They thought that calcium absorption involves

both an active and passive transport mechanisms this may explain that the

Discussion

١١٥

permeability of the small intestine may be increased in some manner by

irradiation and the active transport mechanism may be decreased This

would indicate that changes in absorption after irradiation are related to

functional alterations Kotb et al (1990) attributed the disturbances in

calcium and magnesium metabolism to the insufficient renal function after

irradiation It has previously been observed that calcium homeostasis is

essential for the maintenance of cellular mitosis Induced hypocalcaemia

would be expected to depress mitotic activity and may be partially

responsible for activity of pathological alterations produced by irradiation

It is interesting to note that various radioprotective agents are known to

influence calcium metabolism The redistribution of calcium and

magnesium in tissue organ may response in recovery from radiation-

induced pathology or in repairable damage in biomemebrane and to prevent

irreversible cell damage (Nada et al 2008)

6176 Manganese

The results of the present study showed a significant decrease in Mn

levels in liver organ after irradiation These results are in agreement with

those of Nada and Azab (2005) who reported a significant decrease in Mn

in liver and other organs The decrease of manganese might indirectly

contribute to the decrease of SOD (Pigeolet et al 1990) This idea might

be supported by the well known fact that Mn is present in the active site of

the antioxidant enzyme Mn-SODs Manganese plays important roles in de

novo synthesises of metalloelement-dependent enzymes required for

utilization of oxygen and prevention of O accumulation as well as tissue

repair processes including metalloelement-dependent DNA and RNA repair

are key to the hypothesis that essential metalloelement chelates decrease

andor facilitate recovery from radiation-induced pathology (Sorenson

2002) Facilitated de novo synthesis of SODs and catalase and decreasing

Discussion

١١٦

or preventing formation of these oxygen radicals may account for some of

the recovery from pathological changes associated with irradiation which

cause systemic inflammatory disease and immmuno-incompetency in the

case of whole body irradiation and focal inflammatory disease associated

with local irradiation It has been reported that manganese and its

compound protect from CNS depression induced by ionizing radiation

(Sorenson et al 1990) Manganese has also been found to be effective in

protecting against riboflavin mediated ultraviolet phototoxicity (Ortel et

al 1990) effective in DNA repair (Greenberg et al 1991) radiorecovery

agent from radiation induced loss in body weight (Irving et al 1996)

manganese were also reported to prevent the decrease in leukocytes

induces by irradiation (Matsubara et al 1987 b)

62 The Possible Protective Role of Foeniculum vulgare Mill

Against Radiation On the other hand the present study revealed that long term

pretreatment of Foeniculum vulgare Mill Essential oil (FEO) for 28 days

to irradiated animals induced significant amelioration effects on the tested

parameters It means that FEO has a physiologic antioxidant role

Essential oils as natural sources of phenolic component attract

investigators to evaluate their activity as antioxidants or free radical

scavengers The essential oils of many plants have proven radical-

scavenging and antioxidant properties in the 2 2-diphenyl-1-picrylhydrazyl

(DPPH) radical assay at room temperature (Tomaino et al 2005) The

phenolic compounds are very important plant constituents because of their

scavenging ability due to their hydroxyl groups (Hatano et al 1989) The

phenolic compounds may contribute directly to antioxidative action (Duh

et al 1999) It has been suggested that polyphenolic compounds have

Discussion

١١٧

inhibitory effects on mutagenesis and carcinogenesis in humans when

reach to 10 g daily ingested from a diet rich in fruits and vegetables

(Tanaka et al 1988)

Antioxidant activities of essential oils from aromatic plants are

mainly attributed to the active compounds present in them This can be due

to the high percentage of main constituents but also to the presence of

other constituents in small quantities or to synergy among them (Abdalla

and Roozen 2001) Fennel essential oil has a physiologic antioxidant

activities including the radical scavenging effect inhibition of hydrogen

peroxides H2O2 and Fe chelating activities where it can minimize free

radical which initiate the chain reactions of lipid peroxidation as mentioned

by (Oktay et al 2003 EL-SN and Karakaya 2004 Singh et al 2006)

Fennel was found to exhibit a radical scavenging activity as well as

a total phenolic and total flavonoid content (Faudale et al 2008) This

might be attributed to the biologically active constituents via

phytochemicals including flavanoids terpenoids carotenoids coumarins

curcumines etc This may induce antioxidant status activities such as SOD

GSH and MTs (Cao and Prior 1998 Mantle et al 1998 Soler-Rivas et

al 2000 Koleva et al 2001)

The antioxidant effect is mainly due to phenolic compounds which

are able to donate a hydrogen atom to the free radicals thus stopping the

propagation chain reaction during lipid peroxidation process (Sanchez-

Mareno et al 1998 Yanishlieva and Marinova 1998) These may

explain the significant amelioration of lipid peroxidation induced by

irradiation The volatile oil contain trans-anethole and cis-anethole

Anethole is the principal active component of fennel seeds which exhibited

anticancer activity (Anand et al 2008) The anethole in fennel has

Discussion

١١٨

repeatedly been shown to reduce inflammation and prevent the occurrence

of cancer Researchers have also proposed a biological mechanism that

may explain these anti-inflammatory and anticancer effects This

mechanism involves the shutting down of an intercellular signaling system

called tumor necrosis factor or (TNF)-mediated signaling By shutting

down this signaling process the anethole in fennel prevents activation of a

potentially strong gene-altering and inflammation-triggering molecule

called NF-kappaB The volatile oil has also been shown to be able to

protect the liver of experimental animals from toxic chemical injury

(Chainy et al 2000) these may explain the ameliorating effect of FEO

on transaminases and ALP induced by irradiation

The better antioxidant activity of oil and extract may be due to the

combinatory effect of more than two compounds which are present in

seeds It has been reported that most natural antioxidative compounds work

synergistically (Kamal El-din and Appelqvist 1996 Lu and Foo 1995)

with each other to produce a broad spectrum of antioxidative activities that

creates an effective defense system against free radical attack

Administration of Foeniculum vulgare (fennel) essential oil for 28

days attenuated the effect of gamma radiation induced increase in

transaminases (AST and ALT) and ALP as will as cholesterol and

triglyceride These findings are in accordance with results of Oumlzbek et al

(2003) Oumlzbek et al (2006) Kaneez et al (2005) and Tognolini et al

(2007) who have reported that FEO has a potent hepatoprotective effect

and antithrombotic activity clot destabilizing effect and vaso-relaxant

action Volatile components of fennel seed extracts contain trans-anethole

fenchone methylchavicol limonene α-pinene camphene β-pinene β-

myrcene α-phellandrene 3-carene camphore and cis-anethole (Simandi et

Discussion

١١٩

al 1999) Among these d-limonene and β-myrcene have been shown to

affect liver function D-limonene increases the concentration of reduced

glutathione (GSH) in the liver (Reicks and Crankshaw 1993)

Glutathione in which the N-terminal glutamate is linked to cystine via a

non-α-peptidyle bond is required by several enzymes Glutathione and the

enzyme glutathione reductase participate in the formation of the correct

disulphide bonds of many proteins and polypeptide hormones and

participate in the metabolism of xenobiotics (Rodwell 1993) βndashmyrcine

on the other hand elevates the levels of apoproteins CYP2B1 and CYP2B2

which are subtypes of the P450 enzyme system (De-Oliveira 1997) The

cytochrome P450 (CYP) enzyme system consists of a super family of

hemoproteins that catalyse the oxidative metabolism of a wide variety of

exogenous chemicals including drugs carcinogens fatty acids and

prostaglandins (Shimada et al 1994)

Administration of FEO protects against the endogenous GSH

depletion resulting from irradiation The increased GSH level suggested

that protection of FEO may be mediated through the modulation of cellular

antioxidant levels These results suggested that FEO has a free radical

scavenging activity Many investigators showed that FEO has strong

antioxidant effect (Oktay et al 2003 Singh et al 2006 Birdane et al

2007) through its phenolic compounds Reicks and Crankshaw (1993)

stated that D-limonene increases the concentration of reduced glutathione

(GSH) in the liver The antioxidant species such as anethole β-myrcene

and D-limonene present in fennel as mentioned earlier might also have

interacted with ROS and neutralized them leading to chemo-preventive

effect Therefore a part from the induction of cytochrome p450 and

glutathione-s-transferase enzymes and activation of antioxidant enzymes

fennel might have also contributed to prevention carcinogenesis through

Discussion

١٢٠

scavenging of reactive oxygen species by its antioxidant properties (Singh

and Kale 2008) The radioprotective activity of plant and herbs may be

mediated through several mechanisms since they are complex mixtures of

many chemicals The majority of plants and herbs contain polyphenols

scavenging of radiation induced free radical and elevation of cellular

antioxidants by plants and herbs in irradiated systems could be leading

mechanisms for radioprotection The polyphenols present in the plants and

herbs may up regulate mRNAs of antioxidant enzymes such as catalase

glutathione transferase glutathione peroxidase superoxide dismutase and

thus may counteract the oxidative stress-induced by ionizing radiations

Up-regulation of DNA repair genes may also protect against radiation-

induced damage by bringing error free repair of DNA damage Reduction

in lipid peroxidation and elevation in non-protein sulphydryl groups may

also contribute to some extent to their radioprotective activity The plants

and herb may also inhibit activation of protein kinase C (PKC) mitogen

activated protein kinase (MAPK) cytochrome P-450 nitric oxide and

several other genes that may be responsible for inducing damage after

irradiation (Jagetia 2007)

An increase in the antioxidant enzyme activity and a reduction in the

lipid peroxidation by Foeniculum vulgare FME may result in reducing a

number of deleterious effects due to the accumulation of oxygen radicals

which could exert a beneficial action against pathological alterations (Choi

and Hwang 2004)

In accordance with our results Ibrahim (2008) stated that there were

significant increases over the control in testosterone level in the serum of

rats treated with fennel oil Also Ibrahim (2007b) found that fennel oil

Discussion

١٢١

administration could ameliorate the destructive effect of cigarette smoke in

rat testis

The improvement effect of fennel oil on testicular function as

indicated by the testosterone may be attributed to the powerful active

components of the fennel oil (Parejo et al 2004 Tognolini et al 2006)

In the present study there was a pronounced amelioration in GSH

level in animals supplemented with FEO before irradiation Glutathione is

probably the most important antioxidant present in the cells It protects

cells from damage caused by ROS Therefore enzymes that help to

generate GSH are critical to the bodys ability to protect itself against

oxidation stress Regarding the main principal constituents of Foeniculum

vulgare plants considerable concentrations of essential trace element were

identified These essential trace elements are involved in multiple

biological processes as constituent of enzyme systems including superoxide

dismutase oxido-reductases glutathione peroxidase and metallothionein

(Matsubara 1988 Bettger and ODell 1993 Bedwall et al 1993 Lux

and Naidoo 1995)

Regarding the main principal constituents of Foeniculum vulgare

Mill plants considerable concentrations of essential trace elements were

identified (Zn Cu Fe Se Mg Mn and Ca) These essential trace elements

are involved in multiple biological processes as constituents of enzymes

system including superoxide dismutase (Cu Zn Mn SODs) oxide

reductase glutathione (GSP GSH GST) metallothionein MTs etc

(Sorenson 2002)

Sorenson (1992) has found that iron selenium manganese copper

calcium magnesium and Zinc-complex have found to prevent death in

Discussion

١٢٢

lethality irradiated mice due to facilitation of de novo synthesis of

essentially metalloelemets-dependent enzymes especially metallothioneins

These enzymes play an important role in preventing accumulation of

pathological concentration of oxygen radicals or in repairing damage

caused by irradiation injury MTs antioxidant properties are mainly derived

form sulfhydryl nucleophilicity and from metal complexation MTs are

proteins characterized by high thiol content and bind Zn and Cu it might

be involved in the protection against oxidative stress and can act as free

radical scavengers (Morcillo et al 2000) Since radiation exposure

produces lipid peroxidation and increases in metallothioneins it

hypothesized MTs may be involved in protection against lipid

peroxidation Highly content of iron in FEO may also account for

subsequent de novo synthesis of the iron metalloelements-dependent

enzymes required for biochemical repair and replacement of cellular and

extra-cellular components needed for recovery from radiolytic damage It

has been reported that iron and its complexes protect from ionizing

radiation (Sorenson et al 1990) El-SN and Karakaya (2004) has found

that Foeniculum vulgare has Fe2+ chelating activities and this may

attenuated the accumulation of Fe after irradiation The deficiency of trace

elements may depress the antioxidant defense mechanisms (Kumar and

Shivakumar 1997) erythrocyte production (Morgan et al 1995) and

enhance lipid abnormalities (Vormann et al 1995 Lerma et al 1995

Doullet et al 1998) Magnesium deficiency increased cholesterol

triglyceride phospholipids concentration lipid peroxidation

transaminases Fe and Ca in tissue (Vormann et al 1995 Lerma et al

1995) In the present work gamma irradiation induced a disturbance in Mg

concentration in different organs and change in Ca in other organs This

disturbance could be attenuated by the high contents of Mg and Ca in

Foeniculum vulgar Mill consequently the high contents of Mg and Ca in

Discussion

١٢٣

Foeniculum vulgar Mill may explain the ameliorating effect against lipid

peroxidation induced by irradiation Selenium is an essential element which

mainly functions through selenoprotein such as glutathione peroxidase

(Levander 1987) Selenium has also long been recognized as an element

of importance in liver detoxification functions (Abdulla and Chmielnicka

1990) Selenium has been shown to have radioprotective and antioxidant

properties in animals because it is an essential component of the enzyme

glutathione peroxidase which uses glutathione to neutralize hydrogen

peroxide The highly contents of selenium in Foeniculum vulgar Mill may

explain the ameliorating effect against depleted level of glutathione

induced by irradiation On the basis of the present observation it could be

suggested that Foeniculum vulgare Mill essential oil which contain a

mixture of bioactive compounds as well as essential trace elements could

be of value to stimulate the body self defense mechanisms against oxidative

stress imply the induction of metallothioneins and the maintenance of

glutathione contents in addition to hepato and renoprotective properties

Discussion

١٢٤

Discussion

١٢٥

Gmaha15doc

124


species (ROS) which damage proteins lipids and nucleic acids Because of

the lipid component in the cell membrane lipid peroxidation is reported to

be susceptible to radiation damage

So the present study was performed to detect the role of Foeniculum

vulgare Mill essential oil (250 mgkg bwt) to overcome the hazards of

ionizing radiation The parameters studied in the current work were serum

AST ALT ALP total bilirubin proteins profile (total protein albumin

globulin and AG ratio) cholesterol triglyceride as well as levels of urea

creatinine and testosterone in serum Liver and kidney glutathione (GSH)

content lipid peroxidation (TBARS) and metallothioneins (MTs) levels

were also investigated In addition levels of some trace elements (Fe Cu

Zn Ca Mg Mn and Se) in liver kidney spleen and testis tissues were also

estimated

Male Swiess albino rats (32) were used weighing 120-150g divided

into 4 groups each consists of 8 rats

Group 1 was normal control group (non-irradiated) group 2

consisted of rats subjected to a single dose of whole body gamma

irradiation (65 Gy) and sacrificed after 7 days of irradiation group 3

received Foeniculum vulgare Mill essential oil (FEO) (250 mgkg bwt) for

28 successive days by intra-gastric gavage and group 4 received treatment

FEO for 21 days then was exposed to gamma-radiation (65Gy) followed

by treatment with FEO 7days later to be 28 days as group 3

Gmaha15doc

125

Sacrifice of all animals was performed at the end of the experiment

and blood liver kidney spleen and testis were obtained for determination

of different biochemical parameters

The results of the present study can be summarized as follows

1- Rats exposed to gamma radiation exhibited a profound elevation of

aspartate amontransferase (AST) alkaline phosphatase bilirubin urea and

creatinine levels lipid (cholesterol triglyceride) abnormalities and an

increase in lipid peroxidation and metallothioneins level Noticeable drop

in liver and kidney glutathione content serum total protein albumin and

testosterone levels were also recorded Tissue organs displayed some

changes in trace element concentrations

2- Rats treated with fennel oil before and after whole body gamma

irradiation showed significant modulation in transaminases alkaline

phosphatase bilirubin urea and creatinine lipids and noticeable

improvement in the activity of antioxidants (glutathione metallothioneins)

and protein profile (total protein albumin) Fennel oil was also effective in

minimizing the radiation-induced increase in lipid peroxidation as well as

trace elements alteration in some tissue organs comparing with irradiated

control rats

It could be concluded that Foeniculum vulgare Mill essential oil

exerts a beneficial protective potentials against many radiation-induced

biochemical perturbations and disturbed oxidative stress markers

References

١٢٦

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on inflammatory mediators (SOD MDA TNF-alpha NF-

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بىالملخص العر

التي تضر آلا من ) ذرات أآسجين تفاعلية( التعرض للأشعة المؤينة ينتج عنه شوارد حرة

غشاء نتيجة لوجود المادة الدهنية آمكون اساسى في وآالدهون والأحماض النووية البروتين

ة تكون الدهون الفوق مؤآسدة نتيجة الإشعاع تسبب ضررا آبيرا للخلايا و الأنسجنالخلية فإ

المختلفة

آيلو جرام للى جرام م٢٥٠( ولذلك تهدف هذه الدراسة إلى معرفة دور زيت نبات الشمر

للحد من الآثار الضارة للأشعة المؤينه)جرذانمن وزن ال

إنزيم الفوسفاتيز القلوي ALT AST)(الناقل الأمينى إنزيماتوقد تم قياس مستوى

(ALP)نسبة الجلوبيولين الالبيومينالبروتين الكلى( المحتوى البروتينى البيليروبين الكلى

الكرياتنين الدهون الثلاثية البولينا مستوى الكوليستيرول وآذلك )الألبيومين إلى الجلوبيولين

بعض الدلالات المضادة للأآسدة بالاضافه إلى قياس مصل الدمفي وهرمون التستوستيرون

مستوى في تحدث التيوآذلك دراسة التغيرات ) المختزل و الميتالوثيونينمحتوى الجلوتاثيون(

في الكبد و الكلى مع تقدير ) المواد المتفاعلة مع حمض الثيوبوربيتيورك(الدهون الفوق مؤآسدة

المنجنيز الحديد النحاس الزنك الكالسيوم الماغنسيوم (ةالعناصر الشحيحمعدلات بعض

كبد الكلى الطحال والخصيةفي ال) والسيلينيوم

يتراوح التيمن ذآور الجرذان البيضاء ) ٣٢(وقد تضمنت هذه الدراسة استخدام عدد

) جرذا٨(على تحتوى آل مجموعة أربع مجموعات ووقسمت إلى جرام١٥٠-١٢٠وزنها من

لى تم تعرضها إ جرذان المجموعة الثانية جرذان المجموعة الضابطة الأولىالمجموعه

المجموعة الثالثة أيام من التشعيع٧و تم ذبحها بعد ) جراى٦٥(جرعة مفردة من أشعة جاما

عن طريق يوما متتالي٢٨ لمدة )آجمي جرامل مل٢٥٠ ( نبات الشمرجرذان تمت معالجتها بزيت

٢١ لمدة )آجمي جرامل مل٢٥٠ ( نبات الشمرجرذان تمت معالجتها بزيت المجموعة الرابعة الفم

أيام ٧ثم عولجت مرة أخرى بزيت نبات الشمر لمدة ) جراى٦٥(يوما ثم تم تعرضها لأشعة جاما

)آما في المجموعة الثالثة( يوما ٢٨لتكمل

الطحال و الكلى الكبد وفى نهاية التجربة تم ذبح الجرذان وأخذت عينات من الدم

ختلفة السالف ذآرها سابقاالخصية لتعيين المتغيرات البيوآيميائية الم


خيص نتائج البحث آالاتىويمكن تل

الناقل الأمينى إنزيم ارتفاعا فيقد أظهرت ) جراى٦٥ (للإشعاع تعرضت التي الجرذان -١

)(AST الدهون الثلاثية البولينا الكوليستيرول البيليروبين إنزيم الفوسفاتيز القلوي

و )المواد المتفاعلة مع حمض الثيوبوربيتيورك( مؤآسدة مستوى الدهون الفوق الكرياتنين

ضواانخف والبروتين الكلى والالبيومين ومستوى التستوستيرونالجلوتاثيونبينما الميتالوثيونين

لأشعة التأآسدى الإجهاد العناصر الشحيحة نتيجة فيانخفاضا ملحوظا ومصاحب بتغيرات طفيفة

جاما

ذات دلالة إحصائية الشمر قبل وبعد التعرض للإشعاع نتج عنه تحسن معالجة الجرذان بزيت -٢

ووظائف الكلى ) و البيليروبينالفوسفاتيز القلوي مين للأالاسبرتيت الناقل(بد في إنزيمات الك

المضادة لثلاثية وتحسن ملحوظ في الدلالاتالكوليستيرول والدهون ا )والكرياتنين البولينا(

وأيضا في ) البروتين الكلى والألبومين(والمحتوى البروتينى ) والميتالوثيونينالجلوتاثيون(للأآسدة

خفض مستوى الدهون الفوق مؤآسدة وخلل العناصر الشحيحة في بعض أنسجة الأعضاء مقارنة

بالجرذان المشععة

لبعض بزيت الشمر له دور وقائي ضد الإشعاع المحفزخلصت الدراسة إلى أن المعالجة

لإجهاد التأآسدى البيوآيميائية واالتغيرات

`

المحتمل لنبات الشمر ضد الإشعاع المحفز لبعض الوقائيالدور التغيرات البيوكيميائية في الجرذان البيضاء

فية الماجستير جكجزء متمم للحصول على درالحيوان علم قسمndashسويف بنى جامعةndashرسالة مقدمه إلى كلية العلوم ) علم الحيوان(العلوم

مقدمــة من

محمدمها محمود على

تحـــت إشراف

نور الدين أمين محمد دأ البيولوجيةاء ي الكيمأستاذ

الإشعاعيةالبحوث الدوائية قسم المركز القومي لبحوث وتكنولوجيا الإشعاع

هيئة الطاقة الذرية

أسامة محمد أحمد محمد د الفسيولوجيأستاذ مساعد

الحيوان علمقسم بنى سويف جامعة -كلية العلوم

الرحيم صلاح عبد مانإيد الفسيولوجيأستاذ مساعد

الحيوان علمقسم جامعة بنى سويف-كلية العلوم

علم الحيوانقسم كليــــة العلـــــوم

بنى سويفجامعة

2010

Title of the M Sc Thesis

The Possible Protective Role of Foeniculum vulgare Mill Against Radiation Induced Certain Biochemical

Changes in Albino Rats

Name of Candidate


For Partial Fulfillment of the Master Degree of Science in Zoology

Submitted to Zoology Department Faculty of Science

Beni ndash Suef University

Supervision Committee

1 Prof Dr Nour El-Din Amin Mohamed

3 Dr Eman Salah Abdel-Reheim Assistant Professor of Physiology- Department of Zoology- Faculty of


Professor of Biological chemistry- Drug Radiation Research Department-

National Center for Radiation Research and Technology (NCRRT) - Atomic

Energy Authority

2 Dr Osama Mohamed Ahmed Assistant Professor of Physiology- Department of Zoology- Faculty of







-Haematology




-Radiobiology

-Systemic Zoology

-Neurophysiology




-Biochemistry

-Toxicology


-Muscle Physiology


-Biostatistics




5 5 6 6 6 7 7 8 8 9 10 11 12 13 14 16 17


22 24

25 27 27 28 29 30 31 33 33 34 35 35 36 37



38 40 41 42 43


47


48


48 48 48 48 48 48 49 49 50 50

51 51 51 51 52 52 53 53 53

54 54 54 55 55 56 56 56 58 58 58 59 59 61 61 61 62


63


94


124


126

Arabic summary

Acknowledgement

I












work being











Acknowledgement

I



encouragement












Ii



Ii



List of Tables

Iii

Table

Page


64


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70


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78


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List of Tables

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List of figures

Iv

Figure Page 1 Foeniculum vulgare Mill (Franz et al 2005) 39


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Abstract

V



Introduction

١














El-Dawi 2005)











Introduction

٢











et al 1985)











1994)






Introduction

٣







radicals




















Introduction

٤


















(Sorenson 2002)


٥






















٦

2111 Alpha particle











2112 Beta particles
















٧



















1994)





light (Ng 2003)


٨


























٩


















following







١٠

























al 2002)


١١










irradiation

















١٢








and 4 Gy















control one





١٣










control

















١٤



























١٥




























١٦


LDL-C


















control





rats


١٧











1997)





1999)












١٨




activities























1986)


١٩





























٢٠



testicular tissues





2004)





















٢١




























٢٢




























٢٣





prevented or cured























٢٤




























٢٥





























٢٦




























٢٧



























٢٨



























٢٩



























٣٠



























٣١





























٣٢





















(Whanger 1992)








٣٣



























٣٤


and Holbrook 1992)






















٣٥




























٣٦



























٣٧




























٣٨






(WHO 1993)






















٣٩






















٤٠


















a b


Fang et al 2006)


٤١


























٤٢



















٤٣




























٤٤
























et al 1987)





٤٥





















et al 2007)








٤٦



activities


٤٧


٤٨


٤٩


٥٠


٥١


٥٢


٥٣


٥٤


٥٥


٥٦


٥٧

Aim of the work

٤٧



















٤٨















413 Treatment




gavages

414 Sampling

4141 Blood samples




٤٩




























٥٠








Italy




















٥١













Principle


following reaction-









٥٢

Principle


following reaction








Principle



pH 10







Principle







٥٣






Principle


medium





Principle








following equations

( )




= minus

=minus


٥٤




Principle


23Urease







Biodiagnostic Egypt

Principle






Principle





٥٥









Biodiagnostic Egypt

Principle






2

Peroxidase22

Oxidase


aseGlycerokin

Lipase

++minus+minus+

+minusminus

+minusminus+

+

⎯⎯⎯ rarr⎯

⎯⎯⎯⎯⎯⎯ rarr⎯


⎯⎯ rarr⎯

minusminus






٥٦












rapid cooling








per gm tissue









٥٧




(PH= 85) for 5 min





unbound metal Ag









centrifuge



80






٥٨




Egypt

Principle





















٥٩


















1976)











٦٠










C1 microg X D


Where



D = dilution factor

C1 microg X D





٦١


this table


05

15

4 sec

5

384

029

74

2855

05

2-3

4 sec

5

9-12

0003

013

4227

05

5-7

4 sec

5

4-44

0015

08

2795

05

5-7

4 sec

5

9-12

0029

057

2139

05

4-7

4 sec

5

9-12

0013

022

2139

05

2-4

4 sec

5

8-11

041

18

2483

02

7-11

4 sec

5

8-11

006

15

Wave length ( nm)

Band pass (nm)

Lamp current (mA)

Integration period

Air flow rate (Lm)

Acetylene flow rat

(Lm)

Sensitivity

Flame (mgL)

Furnace (pg)










Jassie 1988)






٦٢











1980)










٦٣


٦٤

Results

٦٣























Results

٦٤



Parameters Groups

AST Ul

ALT Ul

ALP Ul



7606plusmn 134a 5064

2845plusmn 05a 517

2314plusmn 46a 3822


51plusmn 135b 101

2802 plusmn 052a 358

17201plusmn 334b 275


5177plusmn1103b 253

2577plusmn 095b

-473 17404plusmn 406b






0

50

100

150

200

250


Groups

Act

iviti

es (U

I)

AST ALT ALP

a

b b

a a b

b

a

b b

b

ab

Results

٦٥
















respectively




Results

٦٦





219plusmn0071a


180plusmn0055b


168plusmn0044b





0

05

1

15

2

25


Groups

Con

cent

ratio

n (m

gdl

)

Bilirubin

b

a

bb

Results

٦٧


























Results

٦٨


AG ratio Globulin

(gdl) Albumin

(gdl) T-proteins

(gdl) parameter


159plusmn 005a

-479 217plusmn008b

093 288plusmn011c

-1676 505plusmn 019c


123plusmn 003b

-2635 282plusmn012a

3116 335plusmn0073a

318- 618plusmn 020a


122plusmn 021b

-2695 265plusmn0104a

2325 312plusmn005b






0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n(g

dl)


bc

a

ab

a

c

ab

b b

a a

a ab

b

Results

٦٩








bwday)








Results

٧٠


Parameters Groups

Urea (mgdl)

Creatinine (mgdl)


5211 plusmn 146a 4601

1004 plusmn 006a 5786


3338 plusmn 101b 647-

0677 plusmn 057c 645


3494 plusmn 114b -210

0816 plusmn 16b




0

10

20

30

40

50

60


Groups

Con

cent

ratio

ns (m

gdl

)

Urea Creatinine

b

a

bb

ca

cb

10

Results

٧١






group




316 respectively








Results

٧٢




0

20

40

60

80

100

120

140


Groups

Con

cent

ratio

ns (M

gdl

)


c

a

c

b

c

a

c

b

Parameters Groups

Cholesterol mgdl

Triglycerides mgdl


9343 plusmn 138a 12427

11831plusmn 18a 16367


4438 plusmn 14c 653

4345 plusmn 143c -316


7131 plusmn 113b

7117 625 plusmn 132b



Results

٧٣



















Results

٧٤





307plusmn0303c


667plusmn025a


660plusmn009a





0

1

2

3

4

5

6

7

8


Groups

Con

cent

ratio

n (n

gm

l)

Testosterone

b

c

a a

Results

٧٥























Results

٧٦


Parameters


TBARS (nmolg)

MTs (mgg tissue)



5299 plusmn 087c -2927

4689 plusmn 076a 2935

437plusmn 1025a


7467 plusmn 114a

033 3829 plusmn0863bc

563 3850 plusmn 072b


6401plusmn 131b -1456

3945plusmn 099b 883

37 plusmn 077b 3533






0

10

20

30

40

50

60

70

80

90


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

bc b

c

ab b

Results

٧٧













control level










experiment

Results

٧٨


Parameters Groups

GSH (mgg tissue)

TBARS (nmolg)

MTs (mggtissue)



3104 plusmn 0826c -5336

7011plusmn104a 6114

369 plusmn 102a 6727


6490plusmn 152a -248

4500 plusmn 07c 342

2101 plusmn 056c -476


5299 plusmn 095b -2037

5777plusmn041b 3277

24 plusmn 047b 879





0

10

20

30

40

50

60

70

80


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

c

b

bc

a

c b

Results

٧٩




















Results

٨٠



Tissues Groups


3432plusmn056a

1089 2844plusmn06c

-817 3173plusmn145b

911 336 plusmn065a


2948plusmn063b

-475 3287plusmn056a

613 3224plusmn140 b

1085 3076plusmn 056b


3536plusmn047a 1425

303plusmn 055b -216

4524plusmn28a 5557

3415plusmn056a





0

10

20

30

40

50

60


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


ba

ba

bb b

a

bc b

aba

b

a

Results

٨١



















out the experiment

Results

٨٢


Tissues Groups

Liver




3 plusmn 005c -2248

214plusmn 01b 974

467plusmn018b -1661

234 plusmn005a 174


358plusmn009b -749

201plusmn0085b 308

615plusmn019a 982

209 plusmn009b -913


403plusmn012a 413

337plusmn026a 7282

425plusmn011b -2410

237 plusmn011a 304


LSD at the 5 level 031 043 0609 024

LSD at the 1 level 042 0585 0822 0325



0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


ab

cb

a

b b b

a

a

b

a

b

ab a ab

Results

٨٣



















Results

٨٤


Tissues Groups

Liver




18307plusmn31a 12881

16444plusmn171b 31048

7421plusmn301b -309

475plusmn217a 1369


831plusmn073c 386

6938plusmn198c 7319

7698 plusmn092b 052

3772plusmn295b -972


1722plusmn39b 11522

319412plusmn10802a

69733 8584 plusmn 17a

1209 4606plusmn273a


LSD at the 5 level 740 16108 550 690

LSD at the 1 level 994 21732 742 930



0

50

100

150

200

250

300

350


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


c

d

b

ab

ab

ba

c c b

b

b

a

a

a

Results

٨٥

















the experiment

Results

٨٦



Tissues

Groups Liver




1594plusmn616b 2581

30468plusmn1230b 10975

4717plusmn1494c -477

4966plusmn2470b 2219


23542plusmn84a 85 80

26525plusmn125c 8260

55714plusmn1655a 1248

44836plusmn259bc 1032


16025plusmn69b 26 48

50516plusmn1512a

24776 5349plusmn225 ab

799 5913plusmn275a


LSD at the 5 level 19047 34689 5207 6750

LSD at the 1 level 25696 468 7025 9107



0

100

200

300

400

500

600

700


Groups

Con

cent

ratio

n (n

gg

tissu

e)


cb

a

bd

b

c

abcc

a ab

c

bbc

a

Results

٨٧



16)
















Results

٨٨


Tissues Groups

Liver




5849plusmn166b -709

2136plusmn127b 16797

1128plusmn096c

3365 775plusmn071b


6538plusmn133a 384

1003plusmn081c 2583

1257plusmn131b 4893

7161plusmn102c


662plusmn15a 515

404plusmn111a 40784

1326plusmn092a 5711

1039plusmn064a


LSD at the 5 level 394 306 329 230

LSD at the 1 level 5324 413 443 311



0

50

100

150

200

250

300

350

400

450


Groups

Con

cent

artio

n (micro

gg

tiss

ue)


a b a ad

b

c

a

dc b a

db c

a

Results

٨٩



17)















kidney and testis

Results

٩٠


Tissues Groups

Liver





4097plusmn1488c

-1812 41419plusmn49b

-158 3731plusmn1314a


4846plusmn107a 15 89

53465plusmn196b 686

42807plusmn663ab

171 33184plusmn901b


4771plusmn168b 1410

66878plusmn369a 3366

445012plusmn84a 574

37674plusmn1703a


LSD at the 5 level 3737 6783 1908 3485

LSD at the 1 level 5041 9151 2575 4702



0

100

200

300

400

500

600

700

800


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


c bca ab

b

c

b

a

b b ab a

aba

ba

Results

٩١














experiment

Results

٩٢


Tissues Groups

Liver



115plusmn0046b -1353


132plusmn0065a -075


134 plusmn 0021a 075






0

02

04

06

08

1

12

14

16


Groups

Con

cnet

ratio

n (micro

gg

tiss

ue)

Liver

a

b

a a

Results

٩٣


except Se (ngg)


vulgare plants




Element




Discussion

٩٤

























Discussion

٩٥



























1993)

Discussion

٩٦


















2003)










Discussion

٩٧



Missiry et al 1998)

























Discussion

٩٨














the liver













Discussion

٩٩



























Discussion

١٠٠



























Discussion

١٠١




























Discussion

١٠٢


























Discussion

١٠٣



























Discussion

١٠٤









al 2007)


















Discussion

١٠٥






















peroxidation






Discussion

١٠٦



























Discussion

١٠٧













1990)















Discussion

١٠٨



























Discussion

١٠٩




























Discussion

١١٠



















damage








Discussion

١١١












Tatar 1987)





6173 Iron











Discussion

١١٢





























Discussion

١١٣







Gores 1995)





















Discussion

١١٤





























Discussion

١١٥















6176 Manganese














Discussion

١١٦



























Discussion

١١٧



(Tanaka et al 1988)

























Discussion

١١٨




























Discussion

١١٩





























Discussion

١٢٠























and Hwang 2004)




Discussion

١٢١


rat testis















and Naidoo 1995)







(Sorenson 2002)



Discussion

١٢٢






























Discussion

١٢٣

















Discussion

١٢٤

Discussion

١٢٥

Gmaha15doc

124














estimated










Gmaha15doc

125



















control rats




References

١٢٦







17(1) 183-194



Res Technol 212(5) 551-560








Egypt










References

١٢٧











41(7) 926ndash33











71(10) 1397-421








References

١٢٨







Chem 20(4) 470-475





London 2 260









Associat 129(5) 617-620








References

١٢٩



























Res Commum 94(4) 1296-1302

References

١٣٠



159



561-586




Rad Res 159(4) 47-83













207





References

١٣١



882-8



























References

١٣٢




6(2) 111-120





235










Lipid Res 30 1895-1906







Biol Chem 273(9) 5279-87



References

١٣٣



Ther 47(1) 117-136




198




1009-1017


















References

١٣٤


Acta 1001(3) 316-324















Int 47(6) 1019-1027








Med 31(6) 907-917




References

١٣٥








J Androl 4(6) 387-92




328(2) 87-94





annu Conf 1st p-5










16575

References

١٣٦







42(6)1189-94












Nutr 128(5)825-831










References

١٣٧












90




Anim Sci 33(2) 75- 83












References

١٣٨



120



























References

١٣٩



115 85-107











133






Rad Res 37 (5) 1261-1273








References

١٤٠






Elem Res 68(1-2) 25-30














345




Rad Res 45(4) 543-8




References

١٤١


















Food Chem 56(6) 1912-20




Commun 3(5) 257-72







References

١٤٢
















Radiol 59 597-602








2080






References

١٤٣





Gastroenterol 57










J Vet Med 8(4)227-232















References

١٤٤






Surg Res 74(2) 149-154









s112








FEBS lett 281(1-2) 9-19




86



References

١٤٥



Physiol 160(1)1-8



31-8



156-81










7(2)181






Bulletin 37 2016-2021





References

١٤٦







Chem 256(23) 12322-28





Vasc Biol 22(9) 1402-1408




365 (2) 333-342











(CSIR) New Delhi 83

References

١٤٧



No 197 379







Biol 10 62-76



28(1) 163-186
















References

١٤٨


288-93













40(2) 74ndash81



77(7) 780- 794








Biophys 405(2) 170-177



References

١٤٩





13(2)17-25






333




Sci Appli 18(2) 367-384








Biochem 27(23) 8509-8515



671-701



References

١٥٠


Brain Res 606(1) 106-10





97





Chem 42 64- 69



54(2) 481-9















References

١٥١




Sci 60(11) 1125-30

















Rinsho 54(1) 46-51




3381




337-49

References

١٥٢



634-40



Res 119(2) 356-65





70-3






13(3)401-9




60(1-2)139-144



Radic Res 29(2) 93-101




Photomed 8(6) 232-5

References

١٥٣











92(7) 2632-9






843-6













References

١٥٤


667




Biochem 6 577- 581




















86-95



Physiol 166(2) 384-386

References

١٥٥



630-644



43-47






Pharmacol 127(5) 1159-1164






Med 98(4) 463-81



Shams Univ








References

١٥٦





Med 4 2





385ndash391









pp 1



18(1) 162-166






References

١٥٧



Res 111(2) 267-275












105-121








Fed Proc 29(4) 1482-8





References

١٥٨



562(1-3) 129-133










435- 44




Bioch 6 263-268











121(1) 31-8

References

١٥٩




Res 143 316-319




Academy Press



514







Applic 21(2) 515-530




23(2) 153-160


England Wiley 4






References

١٦٠








Sci 22(1) 30-5






Applic 18(2) 335-349




Applic 18(2) 227-293










References

١٦١









New York I 247-285




















7(2) 261-76

References

١٦٢



17(2) 281-295




27(A) 43-55


















52(7) 1890-7





References

١٦٣










51(3) 283-97










62









References

١٦٤






45








Chem 15(2) 997-1003







447-54




91





References

١٦٥






819






30(4) 725-38











USA 33-40




1229-34

References

١٦٦









252-75




















Appplic 2 107-124

References

١٦٧




Exp Biol Med 202(3) 295-301







Zool 28(A) 191-9






Applic 19(2) 433-452








12(4) 251ndash259





References

١٦٨



101-9




82














707-13








References

١٦٩














115-128











306-15




1640-9

References

١٧٠







54(4) 733-6






















6

References

١٧١













31(3) 257-236












Toxicol 46(12) 3842-3850





References

١٧٢


























437-568



References

١٧٣



Chem 9(6) 639-662








78

















References

١٧٤



77-86









659-65













9(1) 23-27




Biol 364(5) 1084-1102

References

١٧٥




Res 32(2) 293-308



320



59(Suppl 5) 401-12



Inst 97 125







Shi 54(8) 1409-1414










References

١٧٦


Applic 19 499-512









Chem 37(17) 2637-2654











17(5) 546-8







References

١٧٧










181-8


Mol Med 6(6) 607-612
















1 753

References

١٧٨









89(2-3) 145ndash154







6(1-2) 681- 688




76(6) 757-762






radiation research




References

١٧٩











Biochem 110(2) 169-173







Biol Chem 284(13) 4793-6



189(1-2) 1-20







References

١٨٠








Ann Arbor














273



In Oil Chem 2 1-14



43(1) 27-32

References

١٨١



Food Chem 42(3) 629-632







Gynecol 135(3) 372-6







Applic 17(1) 47-60










5170



References

١٨٢



Inflamm 2006(5) 1-9





المختلفة




























جاما









`



مقدمــة من












2010






-Haematology




-Radiobiology

-Systemic Zoology

-Neurophysiology




-Biochemistry

-Toxicology


-Muscle Physiology


-Biostatistics




5 5 6 6 6 7 7 8 8 9 10 11 12 13 14 16 17


22 24

25 27 27 28 29 30 31 33 33 34 35 35 36 37



38 40 41 42 43


47


48


48 48 48 48 48 48 49 49 50 50

51 51 51 51 52 52 53 53 53

54 54 54 55 55 56 56 56 58 58 58 59 59 61 61 61 62


63


94


124


126

Arabic summary

Acknowledgement

I












work being











Acknowledgement

I



encouragement












Ii



Ii



List of Tables

Iii

Table

Page


64


66


68


70


72


74


76


78


80


82


84


86

List of Tables

Iii


88


90


92


93

List of figures

Iv



40


42


64


66


68


70


72


74


76


78


80


82


84


86


88


90


92

Abstract

V



Introduction

١














El-Dawi 2005)











Introduction

٢











et al 1985)











1994)






Introduction

٣







radicals




















Introduction

٤


















(Sorenson 2002)


٥






















٦

2111 Alpha particle











2112 Beta particles
















٧



















1994)





light (Ng 2003)


٨


























٩


















following







١٠

























al 2002)


١١










irradiation

















١٢








and 4 Gy















control one





١٣










control

















١٤



























١٥




























١٦


LDL-C


















control





rats


١٧











1997)





1999)












١٨




activities























1986)


١٩





























٢٠



testicular tissues





2004)





















٢١




























٢٢




























٢٣





prevented or cured























٢٤




























٢٥





























٢٦




























٢٧



























٢٨



























٢٩



























٣٠



























٣١





























٣٢





















(Whanger 1992)








٣٣



























٣٤


and Holbrook 1992)






















٣٥




























٣٦



























٣٧




























٣٨






(WHO 1993)






















٣٩






















٤٠


















a b


Fang et al 2006)


٤١


























٤٢



















٤٣




























٤٤
























et al 1987)





٤٥





















et al 2007)








٤٦



activities


٤٧


٤٨


٤٩


٥٠


٥١


٥٢


٥٣


٥٤


٥٥


٥٦


٥٧

Aim of the work

٤٧



















٤٨















413 Treatment




gavages

414 Sampling

4141 Blood samples




٤٩




























٥٠








Italy




















٥١













Principle


following reaction-









٥٢

Principle


following reaction








Principle



pH 10







Principle







٥٣






Principle


medium





Principle








following equations

( )




= minus

=minus


٥٤




Principle


23Urease







Biodiagnostic Egypt

Principle






Principle





٥٥









Biodiagnostic Egypt

Principle






2

Peroxidase22

Oxidase


aseGlycerokin

Lipase

++minus+minus+

+minusminus

+minusminus+

+

⎯⎯⎯ rarr⎯

⎯⎯⎯⎯⎯⎯ rarr⎯


⎯⎯ rarr⎯

minusminus






٥٦












rapid cooling








per gm tissue









٥٧




(PH= 85) for 5 min





unbound metal Ag









centrifuge



80






٥٨




Egypt

Principle





















٥٩


















1976)











٦٠










C1 microg X D


Where



D = dilution factor

C1 microg X D





٦١


this table


05

15

4 sec

5

384

029

74

2855

05

2-3

4 sec

5

9-12

0003

013

4227

05

5-7

4 sec

5

4-44

0015

08

2795

05

5-7

4 sec

5

9-12

0029

057

2139

05

4-7

4 sec

5

9-12

0013

022

2139

05

2-4

4 sec

5

8-11

041

18

2483

02

7-11

4 sec

5

8-11

006

15

Wave length ( nm)

Band pass (nm)

Lamp current (mA)

Integration period

Air flow rate (Lm)

Acetylene flow rat

(Lm)

Sensitivity

Flame (mgL)

Furnace (pg)










Jassie 1988)






٦٢











1980)










٦٣


٦٤

Results

٦٣























Results

٦٤



Parameters Groups

AST Ul

ALT Ul

ALP Ul



7606plusmn 134a 5064

2845plusmn 05a 517

2314plusmn 46a 3822


51plusmn 135b 101

2802 plusmn 052a 358

17201plusmn 334b 275


5177plusmn1103b 253

2577plusmn 095b

-473 17404plusmn 406b






0

50

100

150

200

250


Groups

Act

iviti

es (U

I)

AST ALT ALP

a

b b

a a b

b

a

b b

b

ab

Results

٦٥
















respectively




Results

٦٦





219plusmn0071a


180plusmn0055b


168plusmn0044b





0

05

1

15

2

25


Groups

Con

cent

ratio

n (m

gdl

)

Bilirubin

b

a

bb

Results

٦٧


























Results

٦٨


AG ratio Globulin

(gdl) Albumin

(gdl) T-proteins

(gdl) parameter


159plusmn 005a

-479 217plusmn008b

093 288plusmn011c

-1676 505plusmn 019c


123plusmn 003b

-2635 282plusmn012a

3116 335plusmn0073a

318- 618plusmn 020a


122plusmn 021b

-2695 265plusmn0104a

2325 312plusmn005b






0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n(g

dl)


bc

a

ab

a

c

ab

b b

a a

a ab

b

Results

٦٩








bwday)








Results

٧٠


Parameters Groups

Urea (mgdl)

Creatinine (mgdl)


5211 plusmn 146a 4601

1004 plusmn 006a 5786


3338 plusmn 101b 647-

0677 plusmn 057c 645


3494 plusmn 114b -210

0816 plusmn 16b




0

10

20

30

40

50

60


Groups

Con

cent

ratio

ns (m

gdl

)

Urea Creatinine

b

a

bb

ca

cb

10

Results

٧١






group




316 respectively








Results

٧٢




0

20

40

60

80

100

120

140


Groups

Con

cent

ratio

ns (M

gdl

)


c

a

c

b

c

a

c

b

Parameters Groups

Cholesterol mgdl

Triglycerides mgdl


9343 plusmn 138a 12427

11831plusmn 18a 16367


4438 plusmn 14c 653

4345 plusmn 143c -316


7131 plusmn 113b

7117 625 plusmn 132b



Results

٧٣



















Results

٧٤





307plusmn0303c


667plusmn025a


660plusmn009a





0

1

2

3

4

5

6

7

8


Groups

Con

cent

ratio

n (n

gm

l)

Testosterone

b

c

a a

Results

٧٥























Results

٧٦


Parameters


TBARS (nmolg)

MTs (mgg tissue)



5299 plusmn 087c -2927

4689 plusmn 076a 2935

437plusmn 1025a


7467 plusmn 114a

033 3829 plusmn0863bc

563 3850 plusmn 072b


6401plusmn 131b -1456

3945plusmn 099b 883

37 plusmn 077b 3533






0

10

20

30

40

50

60

70

80

90


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

bc b

c

ab b

Results

٧٧













control level










experiment

Results

٧٨


Parameters Groups

GSH (mgg tissue)

TBARS (nmolg)

MTs (mggtissue)



3104 plusmn 0826c -5336

7011plusmn104a 6114

369 plusmn 102a 6727


6490plusmn 152a -248

4500 plusmn 07c 342

2101 plusmn 056c -476


5299 plusmn 095b -2037

5777plusmn041b 3277

24 plusmn 047b 879





0

10

20

30

40

50

60

70

80


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

c

b

bc

a

c b

Results

٧٩




















Results

٨٠



Tissues Groups


3432plusmn056a

1089 2844plusmn06c

-817 3173plusmn145b

911 336 plusmn065a


2948plusmn063b

-475 3287plusmn056a

613 3224plusmn140 b

1085 3076plusmn 056b


3536plusmn047a 1425

303plusmn 055b -216

4524plusmn28a 5557

3415plusmn056a





0

10

20

30

40

50

60


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


ba

ba

bb b

a

bc b

aba

b

a

Results

٨١



















out the experiment

Results

٨٢


Tissues Groups

Liver




3 plusmn 005c -2248

214plusmn 01b 974

467plusmn018b -1661

234 plusmn005a 174


358plusmn009b -749

201plusmn0085b 308

615plusmn019a 982

209 plusmn009b -913


403plusmn012a 413

337plusmn026a 7282

425plusmn011b -2410

237 plusmn011a 304


LSD at the 5 level 031 043 0609 024

LSD at the 1 level 042 0585 0822 0325



0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


ab

cb

a

b b b

a

a

b

a

b

ab a ab

Results

٨٣



















Results

٨٤


Tissues Groups

Liver




18307plusmn31a 12881

16444plusmn171b 31048

7421plusmn301b -309

475plusmn217a 1369


831plusmn073c 386

6938plusmn198c 7319

7698 plusmn092b 052

3772plusmn295b -972


1722plusmn39b 11522

319412plusmn10802a

69733 8584 plusmn 17a

1209 4606plusmn273a


LSD at the 5 level 740 16108 550 690

LSD at the 1 level 994 21732 742 930



0

50

100

150

200

250

300

350


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


c

d

b

ab

ab

ba

c c b

b

b

a

a

a

Results

٨٥

















the experiment

Results

٨٦



Tissues

Groups Liver




1594plusmn616b 2581

30468plusmn1230b 10975

4717plusmn1494c -477

4966plusmn2470b 2219


23542plusmn84a 85 80

26525plusmn125c 8260

55714plusmn1655a 1248

44836plusmn259bc 1032


16025plusmn69b 26 48

50516plusmn1512a

24776 5349plusmn225 ab

799 5913plusmn275a


LSD at the 5 level 19047 34689 5207 6750

LSD at the 1 level 25696 468 7025 9107



0

100

200

300

400

500

600

700


Groups

Con

cent

ratio

n (n

gg

tissu

e)


cb

a

bd

b

c

abcc

a ab

c

bbc

a

Results

٨٧



16)
















Results

٨٨


Tissues Groups

Liver




5849plusmn166b -709

2136plusmn127b 16797

1128plusmn096c

3365 775plusmn071b


6538plusmn133a 384

1003plusmn081c 2583

1257plusmn131b 4893

7161plusmn102c


662plusmn15a 515

404plusmn111a 40784

1326plusmn092a 5711

1039plusmn064a


LSD at the 5 level 394 306 329 230

LSD at the 1 level 5324 413 443 311



0

50

100

150

200

250

300

350

400

450


Groups

Con

cent

artio

n (micro

gg

tiss

ue)


a b a ad

b

c

a

dc b a

db c

a

Results

٨٩



17)















kidney and testis

Results

٩٠


Tissues Groups

Liver





4097plusmn1488c

-1812 41419plusmn49b

-158 3731plusmn1314a


4846plusmn107a 15 89

53465plusmn196b 686

42807plusmn663ab

171 33184plusmn901b


4771plusmn168b 1410

66878plusmn369a 3366

445012plusmn84a 574

37674plusmn1703a


LSD at the 5 level 3737 6783 1908 3485

LSD at the 1 level 5041 9151 2575 4702



0

100

200

300

400

500

600

700

800


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


c bca ab

b

c

b

a

b b ab a

aba

ba

Results

٩١














experiment

Results

٩٢


Tissues Groups

Liver



115plusmn0046b -1353


132plusmn0065a -075


134 plusmn 0021a 075






0

02

04

06

08

1

12

14

16


Groups

Con

cnet

ratio

n (micro

gg

tiss

ue)

Liver

a

b

a a

Results

٩٣


except Se (ngg)


vulgare plants




Element




Discussion

٩٤

























Discussion

٩٥



























1993)

Discussion

٩٦


















2003)










Discussion

٩٧



Missiry et al 1998)

























Discussion

٩٨














the liver













Discussion

٩٩



























Discussion

١٠٠



























Discussion

١٠١




























Discussion

١٠٢


























Discussion

١٠٣



























Discussion

١٠٤









al 2007)


















Discussion

١٠٥






















peroxidation






Discussion

١٠٦



























Discussion

١٠٧













1990)















Discussion

١٠٨



























Discussion

١٠٩




























Discussion

١١٠



















damage








Discussion

١١١












Tatar 1987)





6173 Iron











Discussion

١١٢





























Discussion

١١٣







Gores 1995)





















Discussion

١١٤





























Discussion

١١٥















6176 Manganese














Discussion

١١٦



























Discussion

١١٧



(Tanaka et al 1988)

























Discussion

١١٨




























Discussion

١١٩





























Discussion

١٢٠























and Hwang 2004)




Discussion

١٢١


rat testis















and Naidoo 1995)







(Sorenson 2002)



Discussion

١٢٢






























Discussion

١٢٣

















Discussion

١٢٤

Discussion

١٢٥

Gmaha15doc

124














estimated










Gmaha15doc

125



















control rats




References

١٢٦







17(1) 183-194



Res Technol 212(5) 551-560








Egypt










References

١٢٧











41(7) 926ndash33











71(10) 1397-421








References

١٢٨







Chem 20(4) 470-475





London 2 260









Associat 129(5) 617-620








References

١٢٩



























Res Commum 94(4) 1296-1302

References

١٣٠



159



561-586




Rad Res 159(4) 47-83













207





References

١٣١



882-8



























References

١٣٢




6(2) 111-120





235










Lipid Res 30 1895-1906







Biol Chem 273(9) 5279-87



References

١٣٣



Ther 47(1) 117-136




198




1009-1017


















References

١٣٤


Acta 1001(3) 316-324















Int 47(6) 1019-1027








Med 31(6) 907-917




References

١٣٥








J Androl 4(6) 387-92




328(2) 87-94





annu Conf 1st p-5










16575

References

١٣٦







42(6)1189-94












Nutr 128(5)825-831










References

١٣٧












90




Anim Sci 33(2) 75- 83












References

١٣٨



120



























References

١٣٩



115 85-107











133






Rad Res 37 (5) 1261-1273








References

١٤٠






Elem Res 68(1-2) 25-30














345




Rad Res 45(4) 543-8




References

١٤١


















Food Chem 56(6) 1912-20




Commun 3(5) 257-72







References

١٤٢
















Radiol 59 597-602








2080






References

١٤٣





Gastroenterol 57










J Vet Med 8(4)227-232















References

١٤٤






Surg Res 74(2) 149-154









s112








FEBS lett 281(1-2) 9-19




86



References

١٤٥



Physiol 160(1)1-8



31-8



156-81










7(2)181






Bulletin 37 2016-2021





References

١٤٦







Chem 256(23) 12322-28





Vasc Biol 22(9) 1402-1408




365 (2) 333-342











(CSIR) New Delhi 83

References

١٤٧



No 197 379







Biol 10 62-76



28(1) 163-186
















References

١٤٨


288-93













40(2) 74ndash81



77(7) 780- 794








Biophys 405(2) 170-177



References

١٤٩





13(2)17-25






333




Sci Appli 18(2) 367-384








Biochem 27(23) 8509-8515



671-701



References

١٥٠


Brain Res 606(1) 106-10





97





Chem 42 64- 69



54(2) 481-9















References

١٥١




Sci 60(11) 1125-30

















Rinsho 54(1) 46-51




3381




337-49

References

١٥٢



634-40



Res 119(2) 356-65





70-3






13(3)401-9




60(1-2)139-144



Radic Res 29(2) 93-101




Photomed 8(6) 232-5

References

١٥٣











92(7) 2632-9






843-6













References

١٥٤


667




Biochem 6 577- 581




















86-95



Physiol 166(2) 384-386

References

١٥٥



630-644



43-47






Pharmacol 127(5) 1159-1164






Med 98(4) 463-81



Shams Univ








References

١٥٦





Med 4 2





385ndash391









pp 1



18(1) 162-166






References

١٥٧



Res 111(2) 267-275












105-121








Fed Proc 29(4) 1482-8





References

١٥٨



562(1-3) 129-133










435- 44




Bioch 6 263-268











121(1) 31-8

References

١٥٩




Res 143 316-319




Academy Press



514







Applic 21(2) 515-530




23(2) 153-160


England Wiley 4






References

١٦٠








Sci 22(1) 30-5






Applic 18(2) 335-349




Applic 18(2) 227-293










References

١٦١









New York I 247-285




















7(2) 261-76

References

١٦٢



17(2) 281-295




27(A) 43-55


















52(7) 1890-7





References

١٦٣










51(3) 283-97










62









References

١٦٤






45








Chem 15(2) 997-1003







447-54




91





References

١٦٥






819






30(4) 725-38











USA 33-40




1229-34

References

١٦٦









252-75




















Appplic 2 107-124

References

١٦٧




Exp Biol Med 202(3) 295-301







Zool 28(A) 191-9






Applic 19(2) 433-452








12(4) 251ndash259





References

١٦٨



101-9




82














707-13








References

١٦٩














115-128











306-15




1640-9

References

١٧٠







54(4) 733-6






















6

References

١٧١













31(3) 257-236












Toxicol 46(12) 3842-3850





References

١٧٢


























437-568



References

١٧٣



Chem 9(6) 639-662








78

















References

١٧٤



77-86









659-65













9(1) 23-27




Biol 364(5) 1084-1102

References

١٧٥




Res 32(2) 293-308



320



59(Suppl 5) 401-12



Inst 97 125







Shi 54(8) 1409-1414










References

١٧٦


Applic 19 499-512









Chem 37(17) 2637-2654











17(5) 546-8







References

١٧٧










181-8


Mol Med 6(6) 607-612
















1 753

References

١٧٨









89(2-3) 145ndash154







6(1-2) 681- 688




76(6) 757-762






radiation research




References

١٧٩











Biochem 110(2) 169-173







Biol Chem 284(13) 4793-6



189(1-2) 1-20







References

١٨٠








Ann Arbor














273



In Oil Chem 2 1-14



43(1) 27-32

References

١٨١



Food Chem 42(3) 629-632







Gynecol 135(3) 372-6







Applic 17(1) 47-60










5170



References

١٨٢



Inflamm 2006(5) 1-9





المختلفة




























جاما









`



مقدمــة من












2010




5 5 6 6 6 7 7 8 8 9 10 11 12 13 14 16 17


22 24

25 27 27 28 29 30 31 33 33 34 35 35 36 37



38 40 41 42 43


47


48


48 48 48 48 48 48 49 49 50 50

51 51 51 51 52 52 53 53 53

54 54 54 55 55 56 56 56 58 58 58 59 59 61 61 61 62


63


94


124


126

Arabic summary

Acknowledgement

I












work being











Acknowledgement

I



encouragement












Ii



Ii



List of Tables

Iii

Table

Page


64


66


68


70


72


74


76


78


80


82


84


86

List of Tables

Iii


88


90


92


93

List of figures

Iv



40


42


64


66


68


70


72


74


76


78


80


82


84


86


88


90


92

Abstract

V



Introduction

١














El-Dawi 2005)











Introduction

٢











et al 1985)











1994)






Introduction

٣







radicals




















Introduction

٤


















(Sorenson 2002)


٥






















٦

2111 Alpha particle











2112 Beta particles
















٧



















1994)





light (Ng 2003)


٨


























٩


















following







١٠

























al 2002)


١١










irradiation

















١٢








and 4 Gy















control one





١٣










control

















١٤



























١٥




























١٦


LDL-C


















control





rats


١٧











1997)





1999)












١٨




activities























1986)


١٩





























٢٠



testicular tissues





2004)





















٢١




























٢٢




























٢٣





prevented or cured























٢٤




























٢٥





























٢٦




























٢٧



























٢٨



























٢٩



























٣٠



























٣١





























٣٢





















(Whanger 1992)








٣٣



























٣٤


and Holbrook 1992)






















٣٥




























٣٦



























٣٧




























٣٨






(WHO 1993)






















٣٩






















٤٠


















a b


Fang et al 2006)


٤١


























٤٢



















٤٣




























٤٤
























et al 1987)





٤٥





















et al 2007)








٤٦



activities


٤٧


٤٨


٤٩


٥٠


٥١


٥٢


٥٣


٥٤


٥٥


٥٦


٥٧

Aim of the work

٤٧



















٤٨















413 Treatment




gavages

414 Sampling

4141 Blood samples




٤٩




























٥٠








Italy




















٥١













Principle


following reaction-









٥٢

Principle


following reaction








Principle



pH 10







Principle







٥٣






Principle


medium





Principle








following equations

( )




= minus

=minus


٥٤




Principle


23Urease







Biodiagnostic Egypt

Principle






Principle





٥٥









Biodiagnostic Egypt

Principle






2

Peroxidase22

Oxidase


aseGlycerokin

Lipase

++minus+minus+

+minusminus

+minusminus+

+

⎯⎯⎯ rarr⎯

⎯⎯⎯⎯⎯⎯ rarr⎯


⎯⎯ rarr⎯

minusminus






٥٦












rapid cooling








per gm tissue









٥٧




(PH= 85) for 5 min





unbound metal Ag









centrifuge



80






٥٨




Egypt

Principle





















٥٩


















1976)











٦٠










C1 microg X D


Where



D = dilution factor

C1 microg X D





٦١


this table


05

15

4 sec

5

384

029

74

2855

05

2-3

4 sec

5

9-12

0003

013

4227

05

5-7

4 sec

5

4-44

0015

08

2795

05

5-7

4 sec

5

9-12

0029

057

2139

05

4-7

4 sec

5

9-12

0013

022

2139

05

2-4

4 sec

5

8-11

041

18

2483

02

7-11

4 sec

5

8-11

006

15

Wave length ( nm)

Band pass (nm)

Lamp current (mA)

Integration period

Air flow rate (Lm)

Acetylene flow rat

(Lm)

Sensitivity

Flame (mgL)

Furnace (pg)










Jassie 1988)






٦٢











1980)










٦٣


٦٤

Results

٦٣























Results

٦٤



Parameters Groups

AST Ul

ALT Ul

ALP Ul



7606plusmn 134a 5064

2845plusmn 05a 517

2314plusmn 46a 3822


51plusmn 135b 101

2802 plusmn 052a 358

17201plusmn 334b 275


5177plusmn1103b 253

2577plusmn 095b

-473 17404plusmn 406b






0

50

100

150

200

250


Groups

Act

iviti

es (U

I)

AST ALT ALP

a

b b

a a b

b

a

b b

b

ab

Results

٦٥
















respectively




Results

٦٦





219plusmn0071a


180plusmn0055b


168plusmn0044b





0

05

1

15

2

25


Groups

Con

cent

ratio

n (m

gdl

)

Bilirubin

b

a

bb

Results

٦٧


























Results

٦٨


AG ratio Globulin

(gdl) Albumin

(gdl) T-proteins

(gdl) parameter


159plusmn 005a

-479 217plusmn008b

093 288plusmn011c

-1676 505plusmn 019c


123plusmn 003b

-2635 282plusmn012a

3116 335plusmn0073a

318- 618plusmn 020a


122plusmn 021b

-2695 265plusmn0104a

2325 312plusmn005b






0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n(g

dl)


bc

a

ab

a

c

ab

b b

a a

a ab

b

Results

٦٩








bwday)








Results

٧٠


Parameters Groups

Urea (mgdl)

Creatinine (mgdl)


5211 plusmn 146a 4601

1004 plusmn 006a 5786


3338 plusmn 101b 647-

0677 plusmn 057c 645


3494 plusmn 114b -210

0816 plusmn 16b




0

10

20

30

40

50

60


Groups

Con

cent

ratio

ns (m

gdl

)

Urea Creatinine

b

a

bb

ca

cb

10

Results

٧١






group




316 respectively








Results

٧٢




0

20

40

60

80

100

120

140


Groups

Con

cent

ratio

ns (M

gdl

)


c

a

c

b

c

a

c

b

Parameters Groups

Cholesterol mgdl

Triglycerides mgdl


9343 plusmn 138a 12427

11831plusmn 18a 16367


4438 plusmn 14c 653

4345 plusmn 143c -316


7131 plusmn 113b

7117 625 plusmn 132b



Results

٧٣



















Results

٧٤





307plusmn0303c


667plusmn025a


660plusmn009a





0

1

2

3

4

5

6

7

8


Groups

Con

cent

ratio

n (n

gm

l)

Testosterone

b

c

a a

Results

٧٥























Results

٧٦


Parameters


TBARS (nmolg)

MTs (mgg tissue)



5299 plusmn 087c -2927

4689 plusmn 076a 2935

437plusmn 1025a


7467 plusmn 114a

033 3829 plusmn0863bc

563 3850 plusmn 072b


6401plusmn 131b -1456

3945plusmn 099b 883

37 plusmn 077b 3533






0

10

20

30

40

50

60

70

80

90


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

bc b

c

ab b

Results

٧٧













control level










experiment

Results

٧٨


Parameters Groups

GSH (mgg tissue)

TBARS (nmolg)

MTs (mggtissue)



3104 plusmn 0826c -5336

7011plusmn104a 6114

369 plusmn 102a 6727


6490plusmn 152a -248

4500 plusmn 07c 342

2101 plusmn 056c -476


5299 plusmn 095b -2037

5777plusmn041b 3277

24 plusmn 047b 879





0

10

20

30

40

50

60

70

80


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

c

b

bc

a

c b

Results

٧٩




















Results

٨٠



Tissues Groups


3432plusmn056a

1089 2844plusmn06c

-817 3173plusmn145b

911 336 plusmn065a


2948plusmn063b

-475 3287plusmn056a

613 3224plusmn140 b

1085 3076plusmn 056b


3536plusmn047a 1425

303plusmn 055b -216

4524plusmn28a 5557

3415plusmn056a





0

10

20

30

40

50

60


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


ba

ba

bb b

a

bc b

aba

b

a

Results

٨١



















out the experiment

Results

٨٢


Tissues Groups

Liver




3 plusmn 005c -2248

214plusmn 01b 974

467plusmn018b -1661

234 plusmn005a 174


358plusmn009b -749

201plusmn0085b 308

615plusmn019a 982

209 plusmn009b -913


403plusmn012a 413

337plusmn026a 7282

425plusmn011b -2410

237 plusmn011a 304


LSD at the 5 level 031 043 0609 024

LSD at the 1 level 042 0585 0822 0325



0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


ab

cb

a

b b b

a

a

b

a

b

ab a ab

Results

٨٣



















Results

٨٤


Tissues Groups

Liver




18307plusmn31a 12881

16444plusmn171b 31048

7421plusmn301b -309

475plusmn217a 1369


831plusmn073c 386

6938plusmn198c 7319

7698 plusmn092b 052

3772plusmn295b -972


1722plusmn39b 11522

319412plusmn10802a

69733 8584 plusmn 17a

1209 4606plusmn273a


LSD at the 5 level 740 16108 550 690

LSD at the 1 level 994 21732 742 930



0

50

100

150

200

250

300

350


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


c

d

b

ab

ab

ba

c c b

b

b

a

a

a

Results

٨٥

















the experiment

Results

٨٦



Tissues

Groups Liver




1594plusmn616b 2581

30468plusmn1230b 10975

4717plusmn1494c -477

4966plusmn2470b 2219


23542plusmn84a 85 80

26525plusmn125c 8260

55714plusmn1655a 1248

44836plusmn259bc 1032


16025plusmn69b 26 48

50516plusmn1512a

24776 5349plusmn225 ab

799 5913plusmn275a


LSD at the 5 level 19047 34689 5207 6750

LSD at the 1 level 25696 468 7025 9107



0

100

200

300

400

500

600

700


Groups

Con

cent

ratio

n (n

gg

tissu

e)


cb

a

bd

b

c

abcc

a ab

c

bbc

a

Results

٨٧



16)
















Results

٨٨


Tissues Groups

Liver




5849plusmn166b -709

2136plusmn127b 16797

1128plusmn096c

3365 775plusmn071b


6538plusmn133a 384

1003plusmn081c 2583

1257plusmn131b 4893

7161plusmn102c


662plusmn15a 515

404plusmn111a 40784

1326plusmn092a 5711

1039plusmn064a


LSD at the 5 level 394 306 329 230

LSD at the 1 level 5324 413 443 311



0

50

100

150

200

250

300

350

400

450


Groups

Con

cent

artio

n (micro

gg

tiss

ue)


a b a ad

b

c

a

dc b a

db c

a

Results

٨٩



17)















kidney and testis

Results

٩٠


Tissues Groups

Liver





4097plusmn1488c

-1812 41419plusmn49b

-158 3731plusmn1314a


4846plusmn107a 15 89

53465plusmn196b 686

42807plusmn663ab

171 33184plusmn901b


4771plusmn168b 1410

66878plusmn369a 3366

445012plusmn84a 574

37674plusmn1703a


LSD at the 5 level 3737 6783 1908 3485

LSD at the 1 level 5041 9151 2575 4702



0

100

200

300

400

500

600

700

800


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


c bca ab

b

c

b

a

b b ab a

aba

ba

Results

٩١














experiment

Results

٩٢


Tissues Groups

Liver



115plusmn0046b -1353


132plusmn0065a -075


134 plusmn 0021a 075






0

02

04

06

08

1

12

14

16


Groups

Con

cnet

ratio

n (micro

gg

tiss

ue)

Liver

a

b

a a

Results

٩٣


except Se (ngg)


vulgare plants




Element




Discussion

٩٤

























Discussion

٩٥



























1993)

Discussion

٩٦


















2003)










Discussion

٩٧



Missiry et al 1998)

























Discussion

٩٨














the liver













Discussion

٩٩



























Discussion

١٠٠



























Discussion

١٠١




























Discussion

١٠٢


























Discussion

١٠٣



























Discussion

١٠٤









al 2007)


















Discussion

١٠٥






















peroxidation






Discussion

١٠٦



























Discussion

١٠٧













1990)















Discussion

١٠٨



























Discussion

١٠٩




























Discussion

١١٠



















damage








Discussion

١١١












Tatar 1987)





6173 Iron











Discussion

١١٢





























Discussion

١١٣







Gores 1995)





















Discussion

١١٤





























Discussion

١١٥















6176 Manganese














Discussion

١١٦



























Discussion

١١٧



(Tanaka et al 1988)

























Discussion

١١٨




























Discussion

١١٩





























Discussion

١٢٠























and Hwang 2004)




Discussion

١٢١


rat testis















and Naidoo 1995)







(Sorenson 2002)



Discussion

١٢٢






























Discussion

١٢٣

















Discussion

١٢٤

Discussion

١٢٥

Gmaha15doc

124














estimated










Gmaha15doc

125



















control rats




References

١٢٦







17(1) 183-194



Res Technol 212(5) 551-560








Egypt










References

١٢٧











41(7) 926ndash33











71(10) 1397-421








References

١٢٨







Chem 20(4) 470-475





London 2 260









Associat 129(5) 617-620








References

١٢٩



























Res Commum 94(4) 1296-1302

References

١٣٠



159



561-586




Rad Res 159(4) 47-83













207





References

١٣١



882-8



























References

١٣٢




6(2) 111-120





235










Lipid Res 30 1895-1906







Biol Chem 273(9) 5279-87



References

١٣٣



Ther 47(1) 117-136




198




1009-1017


















References

١٣٤


Acta 1001(3) 316-324















Int 47(6) 1019-1027








Med 31(6) 907-917




References

١٣٥








J Androl 4(6) 387-92




328(2) 87-94





annu Conf 1st p-5










16575

References

١٣٦







42(6)1189-94












Nutr 128(5)825-831










References

١٣٧












90




Anim Sci 33(2) 75- 83












References

١٣٨



120



























References

١٣٩



115 85-107











133






Rad Res 37 (5) 1261-1273








References

١٤٠






Elem Res 68(1-2) 25-30














345




Rad Res 45(4) 543-8




References

١٤١


















Food Chem 56(6) 1912-20




Commun 3(5) 257-72







References

١٤٢
















Radiol 59 597-602








2080






References

١٤٣





Gastroenterol 57










J Vet Med 8(4)227-232















References

١٤٤






Surg Res 74(2) 149-154









s112








FEBS lett 281(1-2) 9-19




86



References

١٤٥



Physiol 160(1)1-8



31-8



156-81










7(2)181






Bulletin 37 2016-2021





References

١٤٦







Chem 256(23) 12322-28





Vasc Biol 22(9) 1402-1408




365 (2) 333-342











(CSIR) New Delhi 83

References

١٤٧



No 197 379







Biol 10 62-76



28(1) 163-186
















References

١٤٨


288-93













40(2) 74ndash81



77(7) 780- 794








Biophys 405(2) 170-177



References

١٤٩





13(2)17-25






333




Sci Appli 18(2) 367-384








Biochem 27(23) 8509-8515



671-701



References

١٥٠


Brain Res 606(1) 106-10





97





Chem 42 64- 69



54(2) 481-9















References

١٥١




Sci 60(11) 1125-30

















Rinsho 54(1) 46-51




3381




337-49

References

١٥٢



634-40



Res 119(2) 356-65





70-3






13(3)401-9




60(1-2)139-144



Radic Res 29(2) 93-101




Photomed 8(6) 232-5

References

١٥٣











92(7) 2632-9






843-6













References

١٥٤


667




Biochem 6 577- 581




















86-95



Physiol 166(2) 384-386

References

١٥٥



630-644



43-47






Pharmacol 127(5) 1159-1164






Med 98(4) 463-81



Shams Univ








References

١٥٦





Med 4 2





385ndash391









pp 1



18(1) 162-166






References

١٥٧



Res 111(2) 267-275












105-121








Fed Proc 29(4) 1482-8





References

١٥٨



562(1-3) 129-133










435- 44




Bioch 6 263-268











121(1) 31-8

References

١٥٩




Res 143 316-319




Academy Press



514







Applic 21(2) 515-530




23(2) 153-160


England Wiley 4






References

١٦٠








Sci 22(1) 30-5






Applic 18(2) 335-349




Applic 18(2) 227-293










References

١٦١









New York I 247-285




















7(2) 261-76

References

١٦٢



17(2) 281-295




27(A) 43-55


















52(7) 1890-7





References

١٦٣










51(3) 283-97










62









References

١٦٤






45








Chem 15(2) 997-1003







447-54




91





References

١٦٥






819






30(4) 725-38











USA 33-40




1229-34

References

١٦٦









252-75




















Appplic 2 107-124

References

١٦٧




Exp Biol Med 202(3) 295-301







Zool 28(A) 191-9






Applic 19(2) 433-452








12(4) 251ndash259





References

١٦٨



101-9




82














707-13








References

١٦٩














115-128











306-15




1640-9

References

١٧٠







54(4) 733-6






















6

References

١٧١













31(3) 257-236












Toxicol 46(12) 3842-3850





References

١٧٢


























437-568



References

١٧٣



Chem 9(6) 639-662








78

















References

١٧٤



77-86









659-65













9(1) 23-27




Biol 364(5) 1084-1102

References

١٧٥




Res 32(2) 293-308



320



59(Suppl 5) 401-12



Inst 97 125







Shi 54(8) 1409-1414










References

١٧٦


Applic 19 499-512









Chem 37(17) 2637-2654











17(5) 546-8







References

١٧٧










181-8


Mol Med 6(6) 607-612
















1 753

References

١٧٨









89(2-3) 145ndash154







6(1-2) 681- 688




76(6) 757-762






radiation research




References

١٧٩











Biochem 110(2) 169-173







Biol Chem 284(13) 4793-6



189(1-2) 1-20







References

١٨٠








Ann Arbor














273



In Oil Chem 2 1-14



43(1) 27-32

References

١٨١



Food Chem 42(3) 629-632







Gynecol 135(3) 372-6







Applic 17(1) 47-60










5170



References

١٨٢



Inflamm 2006(5) 1-9





المختلفة




























جاما









`



مقدمــة من












2010



38 40 41 42 43


47


48


48 48 48 48 48 48 49 49 50 50

51 51 51 51 52 52 53 53 53

54 54 54 55 55 56 56 56 58 58 58 59 59 61 61 61 62


63


94


124


126

Arabic summary

Acknowledgement

I












work being











Acknowledgement

I



encouragement












Ii



Ii



List of Tables

Iii

Table

Page


64


66


68


70


72


74


76


78


80


82


84


86

List of Tables

Iii


88


90


92


93

List of figures

Iv



40


42


64


66


68


70


72


74


76


78


80


82


84


86


88


90


92

Abstract

V



Introduction

١














El-Dawi 2005)











Introduction

٢











et al 1985)











1994)






Introduction

٣







radicals




















Introduction

٤


















(Sorenson 2002)


٥






















٦

2111 Alpha particle











2112 Beta particles
















٧



















1994)





light (Ng 2003)


٨


























٩


















following







١٠

























al 2002)


١١










irradiation

















١٢








and 4 Gy















control one





١٣










control

















١٤



























١٥




























١٦


LDL-C


















control





rats


١٧











1997)





1999)












١٨




activities























1986)


١٩





























٢٠



testicular tissues





2004)





















٢١




























٢٢




























٢٣





prevented or cured























٢٤




























٢٥





























٢٦




























٢٧



























٢٨



























٢٩



























٣٠



























٣١





























٣٢





















(Whanger 1992)








٣٣



























٣٤


and Holbrook 1992)






















٣٥




























٣٦



























٣٧




























٣٨






(WHO 1993)






















٣٩






















٤٠


















a b


Fang et al 2006)


٤١


























٤٢



















٤٣




























٤٤
























et al 1987)





٤٥





















et al 2007)








٤٦



activities


٤٧


٤٨


٤٩


٥٠


٥١


٥٢


٥٣


٥٤


٥٥


٥٦


٥٧

Aim of the work

٤٧



















٤٨















413 Treatment




gavages

414 Sampling

4141 Blood samples




٤٩




























٥٠








Italy




















٥١













Principle


following reaction-









٥٢

Principle


following reaction








Principle



pH 10







Principle







٥٣






Principle


medium





Principle








following equations

( )




= minus

=minus


٥٤




Principle


23Urease







Biodiagnostic Egypt

Principle






Principle





٥٥









Biodiagnostic Egypt

Principle






2

Peroxidase22

Oxidase


aseGlycerokin

Lipase

++minus+minus+

+minusminus

+minusminus+

+

⎯⎯⎯ rarr⎯

⎯⎯⎯⎯⎯⎯ rarr⎯


⎯⎯ rarr⎯

minusminus






٥٦












rapid cooling








per gm tissue









٥٧




(PH= 85) for 5 min





unbound metal Ag









centrifuge



80






٥٨




Egypt

Principle





















٥٩


















1976)











٦٠










C1 microg X D


Where



D = dilution factor

C1 microg X D





٦١


this table


05

15

4 sec

5

384

029

74

2855

05

2-3

4 sec

5

9-12

0003

013

4227

05

5-7

4 sec

5

4-44

0015

08

2795

05

5-7

4 sec

5

9-12

0029

057

2139

05

4-7

4 sec

5

9-12

0013

022

2139

05

2-4

4 sec

5

8-11

041

18

2483

02

7-11

4 sec

5

8-11

006

15

Wave length ( nm)

Band pass (nm)

Lamp current (mA)

Integration period

Air flow rate (Lm)

Acetylene flow rat

(Lm)

Sensitivity

Flame (mgL)

Furnace (pg)










Jassie 1988)






٦٢











1980)










٦٣


٦٤

Results

٦٣























Results

٦٤



Parameters Groups

AST Ul

ALT Ul

ALP Ul



7606plusmn 134a 5064

2845plusmn 05a 517

2314plusmn 46a 3822


51plusmn 135b 101

2802 plusmn 052a 358

17201plusmn 334b 275


5177plusmn1103b 253

2577plusmn 095b

-473 17404plusmn 406b






0

50

100

150

200

250


Groups

Act

iviti

es (U

I)

AST ALT ALP

a

b b

a a b

b

a

b b

b

ab

Results

٦٥
















respectively




Results

٦٦





219plusmn0071a


180plusmn0055b


168plusmn0044b





0

05

1

15

2

25


Groups

Con

cent

ratio

n (m

gdl

)

Bilirubin

b

a

bb

Results

٦٧


























Results

٦٨


AG ratio Globulin

(gdl) Albumin

(gdl) T-proteins

(gdl) parameter


159plusmn 005a

-479 217plusmn008b

093 288plusmn011c

-1676 505plusmn 019c


123plusmn 003b

-2635 282plusmn012a

3116 335plusmn0073a

318- 618plusmn 020a


122plusmn 021b

-2695 265plusmn0104a

2325 312plusmn005b






0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n(g

dl)


bc

a

ab

a

c

ab

b b

a a

a ab

b

Results

٦٩








bwday)








Results

٧٠


Parameters Groups

Urea (mgdl)

Creatinine (mgdl)


5211 plusmn 146a 4601

1004 plusmn 006a 5786


3338 plusmn 101b 647-

0677 plusmn 057c 645


3494 plusmn 114b -210

0816 plusmn 16b




0

10

20

30

40

50

60


Groups

Con

cent

ratio

ns (m

gdl

)

Urea Creatinine

b

a

bb

ca

cb

10

Results

٧١






group




316 respectively








Results

٧٢




0

20

40

60

80

100

120

140


Groups

Con

cent

ratio

ns (M

gdl

)


c

a

c

b

c

a

c

b

Parameters Groups

Cholesterol mgdl

Triglycerides mgdl


9343 plusmn 138a 12427

11831plusmn 18a 16367


4438 plusmn 14c 653

4345 plusmn 143c -316


7131 plusmn 113b

7117 625 plusmn 132b



Results

٧٣



















Results

٧٤





307plusmn0303c


667plusmn025a


660plusmn009a





0

1

2

3

4

5

6

7

8


Groups

Con

cent

ratio

n (n

gm

l)

Testosterone

b

c

a a

Results

٧٥























Results

٧٦


Parameters


TBARS (nmolg)

MTs (mgg tissue)



5299 plusmn 087c -2927

4689 plusmn 076a 2935

437plusmn 1025a


7467 plusmn 114a

033 3829 plusmn0863bc

563 3850 plusmn 072b


6401plusmn 131b -1456

3945plusmn 099b 883

37 plusmn 077b 3533






0

10

20

30

40

50

60

70

80

90


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

bc b

c

ab b

Results

٧٧













control level










experiment

Results

٧٨


Parameters Groups

GSH (mgg tissue)

TBARS (nmolg)

MTs (mggtissue)



3104 plusmn 0826c -5336

7011plusmn104a 6114

369 plusmn 102a 6727


6490plusmn 152a -248

4500 plusmn 07c 342

2101 plusmn 056c -476


5299 plusmn 095b -2037

5777plusmn041b 3277

24 plusmn 047b 879





0

10

20

30

40

50

60

70

80


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

c

b

bc

a

c b

Results

٧٩




















Results

٨٠



Tissues Groups


3432plusmn056a

1089 2844plusmn06c

-817 3173plusmn145b

911 336 plusmn065a


2948plusmn063b

-475 3287plusmn056a

613 3224plusmn140 b

1085 3076plusmn 056b


3536plusmn047a 1425

303plusmn 055b -216

4524plusmn28a 5557

3415plusmn056a





0

10

20

30

40

50

60


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


ba

ba

bb b

a

bc b

aba

b

a

Results

٨١



















out the experiment

Results

٨٢


Tissues Groups

Liver




3 plusmn 005c -2248

214plusmn 01b 974

467plusmn018b -1661

234 plusmn005a 174


358plusmn009b -749

201plusmn0085b 308

615plusmn019a 982

209 plusmn009b -913


403plusmn012a 413

337plusmn026a 7282

425plusmn011b -2410

237 plusmn011a 304


LSD at the 5 level 031 043 0609 024

LSD at the 1 level 042 0585 0822 0325



0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


ab

cb

a

b b b

a

a

b

a

b

ab a ab

Results

٨٣



















Results

٨٤


Tissues Groups

Liver




18307plusmn31a 12881

16444plusmn171b 31048

7421plusmn301b -309

475plusmn217a 1369


831plusmn073c 386

6938plusmn198c 7319

7698 plusmn092b 052

3772plusmn295b -972


1722plusmn39b 11522

319412plusmn10802a

69733 8584 plusmn 17a

1209 4606plusmn273a


LSD at the 5 level 740 16108 550 690

LSD at the 1 level 994 21732 742 930



0

50

100

150

200

250

300

350


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


c

d

b

ab

ab

ba

c c b

b

b

a

a

a

Results

٨٥

















the experiment

Results

٨٦



Tissues

Groups Liver




1594plusmn616b 2581

30468plusmn1230b 10975

4717plusmn1494c -477

4966plusmn2470b 2219


23542plusmn84a 85 80

26525plusmn125c 8260

55714plusmn1655a 1248

44836plusmn259bc 1032


16025plusmn69b 26 48

50516plusmn1512a

24776 5349plusmn225 ab

799 5913plusmn275a


LSD at the 5 level 19047 34689 5207 6750

LSD at the 1 level 25696 468 7025 9107



0

100

200

300

400

500

600

700


Groups

Con

cent

ratio

n (n

gg

tissu

e)


cb

a

bd

b

c

abcc

a ab

c

bbc

a

Results

٨٧



16)
















Results

٨٨


Tissues Groups

Liver




5849plusmn166b -709

2136plusmn127b 16797

1128plusmn096c

3365 775plusmn071b


6538plusmn133a 384

1003plusmn081c 2583

1257plusmn131b 4893

7161plusmn102c


662plusmn15a 515

404plusmn111a 40784

1326plusmn092a 5711

1039plusmn064a


LSD at the 5 level 394 306 329 230

LSD at the 1 level 5324 413 443 311



0

50

100

150

200

250

300

350

400

450


Groups

Con

cent

artio

n (micro

gg

tiss

ue)


a b a ad

b

c

a

dc b a

db c

a

Results

٨٩



17)















kidney and testis

Results

٩٠


Tissues Groups

Liver





4097plusmn1488c

-1812 41419plusmn49b

-158 3731plusmn1314a


4846plusmn107a 15 89

53465plusmn196b 686

42807plusmn663ab

171 33184plusmn901b


4771plusmn168b 1410

66878plusmn369a 3366

445012plusmn84a 574

37674plusmn1703a


LSD at the 5 level 3737 6783 1908 3485

LSD at the 1 level 5041 9151 2575 4702



0

100

200

300

400

500

600

700

800


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


c bca ab

b

c

b

a

b b ab a

aba

ba

Results

٩١














experiment

Results

٩٢


Tissues Groups

Liver



115plusmn0046b -1353


132plusmn0065a -075


134 plusmn 0021a 075






0

02

04

06

08

1

12

14

16


Groups

Con

cnet

ratio

n (micro

gg

tiss

ue)

Liver

a

b

a a

Results

٩٣


except Se (ngg)


vulgare plants




Element




Discussion

٩٤

























Discussion

٩٥



























1993)

Discussion

٩٦


















2003)










Discussion

٩٧



Missiry et al 1998)

























Discussion

٩٨














the liver













Discussion

٩٩



























Discussion

١٠٠



























Discussion

١٠١




























Discussion

١٠٢


























Discussion

١٠٣



























Discussion

١٠٤









al 2007)


















Discussion

١٠٥






















peroxidation






Discussion

١٠٦



























Discussion

١٠٧













1990)















Discussion

١٠٨



























Discussion

١٠٩




























Discussion

١١٠



















damage








Discussion

١١١












Tatar 1987)





6173 Iron











Discussion

١١٢





























Discussion

١١٣







Gores 1995)





















Discussion

١١٤





























Discussion

١١٥















6176 Manganese














Discussion

١١٦



























Discussion

١١٧



(Tanaka et al 1988)

























Discussion

١١٨




























Discussion

١١٩





























Discussion

١٢٠























and Hwang 2004)




Discussion

١٢١


rat testis















and Naidoo 1995)







(Sorenson 2002)



Discussion

١٢٢






























Discussion

١٢٣

















Discussion

١٢٤

Discussion

١٢٥

Gmaha15doc

124














estimated










Gmaha15doc

125



















control rats




References

١٢٦







17(1) 183-194



Res Technol 212(5) 551-560








Egypt










References

١٢٧











41(7) 926ndash33











71(10) 1397-421








References

١٢٨







Chem 20(4) 470-475





London 2 260









Associat 129(5) 617-620








References

١٢٩



























Res Commum 94(4) 1296-1302

References

١٣٠



159



561-586




Rad Res 159(4) 47-83













207





References

١٣١



882-8



























References

١٣٢




6(2) 111-120





235










Lipid Res 30 1895-1906







Biol Chem 273(9) 5279-87



References

١٣٣



Ther 47(1) 117-136




198




1009-1017


















References

١٣٤


Acta 1001(3) 316-324















Int 47(6) 1019-1027








Med 31(6) 907-917




References

١٣٥








J Androl 4(6) 387-92




328(2) 87-94





annu Conf 1st p-5










16575

References

١٣٦







42(6)1189-94












Nutr 128(5)825-831










References

١٣٧












90




Anim Sci 33(2) 75- 83












References

١٣٨



120



























References

١٣٩



115 85-107











133






Rad Res 37 (5) 1261-1273








References

١٤٠






Elem Res 68(1-2) 25-30














345




Rad Res 45(4) 543-8




References

١٤١


















Food Chem 56(6) 1912-20




Commun 3(5) 257-72







References

١٤٢
















Radiol 59 597-602








2080






References

١٤٣





Gastroenterol 57










J Vet Med 8(4)227-232















References

١٤٤






Surg Res 74(2) 149-154









s112








FEBS lett 281(1-2) 9-19




86



References

١٤٥



Physiol 160(1)1-8



31-8



156-81










7(2)181






Bulletin 37 2016-2021





References

١٤٦







Chem 256(23) 12322-28





Vasc Biol 22(9) 1402-1408




365 (2) 333-342











(CSIR) New Delhi 83

References

١٤٧



No 197 379







Biol 10 62-76



28(1) 163-186
















References

١٤٨


288-93













40(2) 74ndash81



77(7) 780- 794








Biophys 405(2) 170-177



References

١٤٩





13(2)17-25






333




Sci Appli 18(2) 367-384








Biochem 27(23) 8509-8515



671-701



References

١٥٠


Brain Res 606(1) 106-10





97





Chem 42 64- 69



54(2) 481-9















References

١٥١




Sci 60(11) 1125-30

















Rinsho 54(1) 46-51




3381




337-49

References

١٥٢



634-40



Res 119(2) 356-65





70-3






13(3)401-9




60(1-2)139-144



Radic Res 29(2) 93-101




Photomed 8(6) 232-5

References

١٥٣











92(7) 2632-9






843-6













References

١٥٤


667




Biochem 6 577- 581




















86-95



Physiol 166(2) 384-386

References

١٥٥



630-644



43-47






Pharmacol 127(5) 1159-1164






Med 98(4) 463-81



Shams Univ








References

١٥٦





Med 4 2





385ndash391









pp 1



18(1) 162-166






References

١٥٧



Res 111(2) 267-275












105-121








Fed Proc 29(4) 1482-8





References

١٥٨



562(1-3) 129-133










435- 44




Bioch 6 263-268











121(1) 31-8

References

١٥٩




Res 143 316-319




Academy Press



514







Applic 21(2) 515-530




23(2) 153-160


England Wiley 4






References

١٦٠








Sci 22(1) 30-5






Applic 18(2) 335-349




Applic 18(2) 227-293










References

١٦١









New York I 247-285




















7(2) 261-76

References

١٦٢



17(2) 281-295




27(A) 43-55


















52(7) 1890-7





References

١٦٣










51(3) 283-97










62









References

١٦٤






45








Chem 15(2) 997-1003







447-54




91





References

١٦٥






819






30(4) 725-38











USA 33-40




1229-34

References

١٦٦









252-75




















Appplic 2 107-124

References

١٦٧




Exp Biol Med 202(3) 295-301







Zool 28(A) 191-9






Applic 19(2) 433-452








12(4) 251ndash259





References

١٦٨



101-9




82














707-13








References

١٦٩














115-128











306-15




1640-9

References

١٧٠







54(4) 733-6






















6

References

١٧١













31(3) 257-236












Toxicol 46(12) 3842-3850





References

١٧٢


























437-568



References

١٧٣



Chem 9(6) 639-662








78

















References

١٧٤



77-86









659-65













9(1) 23-27




Biol 364(5) 1084-1102

References

١٧٥




Res 32(2) 293-308



320



59(Suppl 5) 401-12



Inst 97 125







Shi 54(8) 1409-1414










References

١٧٦


Applic 19 499-512









Chem 37(17) 2637-2654











17(5) 546-8







References

١٧٧










181-8


Mol Med 6(6) 607-612
















1 753

References

١٧٨









89(2-3) 145ndash154







6(1-2) 681- 688




76(6) 757-762






radiation research




References

١٧٩











Biochem 110(2) 169-173







Biol Chem 284(13) 4793-6



189(1-2) 1-20







References

١٨٠








Ann Arbor














273



In Oil Chem 2 1-14



43(1) 27-32

References

١٨١



Food Chem 42(3) 629-632







Gynecol 135(3) 372-6







Applic 17(1) 47-60










5170



References

١٨٢



Inflamm 2006(5) 1-9





المختلفة




























جاما









`



مقدمــة من












2010


63


94


124


126

Arabic summary

Acknowledgement

I












work being











Acknowledgement

I



encouragement












Ii



Ii



List of Tables

Iii

Table

Page


64


66


68


70


72


74


76


78


80


82


84


86

List of Tables

Iii


88


90


92


93

List of figures

Iv



40


42


64


66


68


70


72


74


76


78


80


82


84


86


88


90


92

Abstract

V



Introduction

١














El-Dawi 2005)











Introduction

٢











et al 1985)











1994)






Introduction

٣







radicals




















Introduction

٤


















(Sorenson 2002)


٥






















٦

2111 Alpha particle











2112 Beta particles
















٧



















1994)





light (Ng 2003)


٨


























٩


















following







١٠

























al 2002)


١١










irradiation

















١٢








and 4 Gy















control one





١٣










control

















١٤



























١٥




























١٦


LDL-C


















control





rats


١٧











1997)





1999)












١٨




activities























1986)


١٩





























٢٠



testicular tissues





2004)





















٢١




























٢٢




























٢٣





prevented or cured























٢٤




























٢٥





























٢٦




























٢٧



























٢٨



























٢٩



























٣٠



























٣١





























٣٢





















(Whanger 1992)








٣٣



























٣٤


and Holbrook 1992)






















٣٥




























٣٦



























٣٧




























٣٨






(WHO 1993)






















٣٩






















٤٠


















a b


Fang et al 2006)


٤١


























٤٢



















٤٣




























٤٤
























et al 1987)





٤٥





















et al 2007)








٤٦



activities


٤٧


٤٨


٤٩


٥٠


٥١


٥٢


٥٣


٥٤


٥٥


٥٦


٥٧

Aim of the work

٤٧



















٤٨















413 Treatment




gavages

414 Sampling

4141 Blood samples




٤٩




























٥٠








Italy




















٥١













Principle


following reaction-









٥٢

Principle


following reaction








Principle



pH 10







Principle







٥٣






Principle


medium





Principle








following equations

( )




= minus

=minus


٥٤




Principle


23Urease







Biodiagnostic Egypt

Principle






Principle





٥٥









Biodiagnostic Egypt

Principle






2

Peroxidase22

Oxidase


aseGlycerokin

Lipase

++minus+minus+

+minusminus

+minusminus+

+

⎯⎯⎯ rarr⎯

⎯⎯⎯⎯⎯⎯ rarr⎯


⎯⎯ rarr⎯

minusminus






٥٦












rapid cooling








per gm tissue









٥٧




(PH= 85) for 5 min





unbound metal Ag









centrifuge



80






٥٨




Egypt

Principle





















٥٩


















1976)











٦٠










C1 microg X D


Where



D = dilution factor

C1 microg X D





٦١


this table


05

15

4 sec

5

384

029

74

2855

05

2-3

4 sec

5

9-12

0003

013

4227

05

5-7

4 sec

5

4-44

0015

08

2795

05

5-7

4 sec

5

9-12

0029

057

2139

05

4-7

4 sec

5

9-12

0013

022

2139

05

2-4

4 sec

5

8-11

041

18

2483

02

7-11

4 sec

5

8-11

006

15

Wave length ( nm)

Band pass (nm)

Lamp current (mA)

Integration period

Air flow rate (Lm)

Acetylene flow rat

(Lm)

Sensitivity

Flame (mgL)

Furnace (pg)










Jassie 1988)






٦٢











1980)










٦٣


٦٤

Results

٦٣























Results

٦٤



Parameters Groups

AST Ul

ALT Ul

ALP Ul



7606plusmn 134a 5064

2845plusmn 05a 517

2314plusmn 46a 3822


51plusmn 135b 101

2802 plusmn 052a 358

17201plusmn 334b 275


5177plusmn1103b 253

2577plusmn 095b

-473 17404plusmn 406b






0

50

100

150

200

250


Groups

Act

iviti

es (U

I)

AST ALT ALP

a

b b

a a b

b

a

b b

b

ab

Results

٦٥
















respectively




Results

٦٦





219plusmn0071a


180plusmn0055b


168plusmn0044b





0

05

1

15

2

25


Groups

Con

cent

ratio

n (m

gdl

)

Bilirubin

b

a

bb

Results

٦٧


























Results

٦٨


AG ratio Globulin

(gdl) Albumin

(gdl) T-proteins

(gdl) parameter


159plusmn 005a

-479 217plusmn008b

093 288plusmn011c

-1676 505plusmn 019c


123plusmn 003b

-2635 282plusmn012a

3116 335plusmn0073a

318- 618plusmn 020a


122plusmn 021b

-2695 265plusmn0104a

2325 312plusmn005b






0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n(g

dl)


bc

a

ab

a

c

ab

b b

a a

a ab

b

Results

٦٩








bwday)








Results

٧٠


Parameters Groups

Urea (mgdl)

Creatinine (mgdl)


5211 plusmn 146a 4601

1004 plusmn 006a 5786


3338 plusmn 101b 647-

0677 plusmn 057c 645


3494 plusmn 114b -210

0816 plusmn 16b




0

10

20

30

40

50

60


Groups

Con

cent

ratio

ns (m

gdl

)

Urea Creatinine

b

a

bb

ca

cb

10

Results

٧١






group




316 respectively








Results

٧٢




0

20

40

60

80

100

120

140


Groups

Con

cent

ratio

ns (M

gdl

)


c

a

c

b

c

a

c

b

Parameters Groups

Cholesterol mgdl

Triglycerides mgdl


9343 plusmn 138a 12427

11831plusmn 18a 16367


4438 plusmn 14c 653

4345 plusmn 143c -316


7131 plusmn 113b

7117 625 plusmn 132b



Results

٧٣



















Results

٧٤





307plusmn0303c


667plusmn025a


660plusmn009a





0

1

2

3

4

5

6

7

8


Groups

Con

cent

ratio

n (n

gm

l)

Testosterone

b

c

a a

Results

٧٥























Results

٧٦


Parameters


TBARS (nmolg)

MTs (mgg tissue)



5299 plusmn 087c -2927

4689 plusmn 076a 2935

437plusmn 1025a


7467 plusmn 114a

033 3829 plusmn0863bc

563 3850 plusmn 072b


6401plusmn 131b -1456

3945plusmn 099b 883

37 plusmn 077b 3533






0

10

20

30

40

50

60

70

80

90


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

bc b

c

ab b

Results

٧٧













control level










experiment

Results

٧٨


Parameters Groups

GSH (mgg tissue)

TBARS (nmolg)

MTs (mggtissue)



3104 plusmn 0826c -5336

7011plusmn104a 6114

369 plusmn 102a 6727


6490plusmn 152a -248

4500 plusmn 07c 342

2101 plusmn 056c -476


5299 plusmn 095b -2037

5777plusmn041b 3277

24 plusmn 047b 879





0

10

20

30

40

50

60

70

80


Groups

Con

cent

ratio

ns


a

c

a

b

c

a

c

b

bc

a

c b

Results

٧٩




















Results

٨٠



Tissues Groups


3432plusmn056a

1089 2844plusmn06c

-817 3173plusmn145b

911 336 plusmn065a


2948plusmn063b

-475 3287plusmn056a

613 3224plusmn140 b

1085 3076plusmn 056b


3536plusmn047a 1425

303plusmn 055b -216

4524plusmn28a 5557

3415plusmn056a





0

10

20

30

40

50

60


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


ba

ba

bb b

a

bc b

aba

b

a

Results

٨١



















out the experiment

Results

٨٢


Tissues Groups

Liver




3 plusmn 005c -2248

214plusmn 01b 974

467plusmn018b -1661

234 plusmn005a 174


358plusmn009b -749

201plusmn0085b 308

615plusmn019a 982

209 plusmn009b -913


403plusmn012a 413

337plusmn026a 7282

425plusmn011b -2410

237 plusmn011a 304


LSD at the 5 level 031 043 0609 024

LSD at the 1 level 042 0585 0822 0325



0

1

2

3

4

5

6

7


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


ab

cb

a

b b b

a

a

b

a

b

ab a ab

Results

٨٣



















Results

٨٤


Tissues Groups

Liver




18307plusmn31a 12881

16444plusmn171b 31048

7421plusmn301b -309

475plusmn217a 1369


831plusmn073c 386

6938plusmn198c 7319

7698 plusmn092b 052

3772plusmn295b -972


1722plusmn39b 11522

319412plusmn10802a

69733 8584 plusmn 17a

1209 4606plusmn273a


LSD at the 5 level 740 16108 550 690

LSD at the 1 level 994 21732 742 930



0

50

100

150

200

250

300

350


Groups

Con

cent

ratio

n (micro

gg

tiss

ue)


c

d

b

ab

ab

ba

c c b

b

b

a

a

a

Results

٨٥

















the experiment

Results

٨٦



Tissues

Groups Liver




1594plusmn616b 2581

30468plusmn1230b 10975

4717plusmn1494c -477

4966plusmn2470b 2219


23542plusmn84a 85 80

26525plusmn125c 8260

55714plusmn1655a 1248

44836plusmn259bc 1032


16025plusmn69b 26 48

50516plusmn1512a

24776 5349plusmn225 ab

799 5913plusmn275a


LSD at the 5 level 19047 34689 5207 6750

LSD at the 1 level 25696 468 7025 9107



0

100

200

300

400

500

600

700


Groups

Con

cent

ratio

n (n

gg

tissu

e)


cb

a

bd

b

c

abcc

a ab

c

bbc

a

Results

٨٧



16)
















Results

٨٨


Tissues Groups

Liver




5849plusmn166b -709

2136plusmn127b 16797

1128plusmn096c

3365 775plusmn071b


6538plusmn133a 384

1003plusmn081c 2583

1257plusmn131b 4893

7161plusmn102c


662plusmn15a 515

404plusmn111a 40784

1326plusmn092a 5711

1039plusmn064a


LSD at the 5 level 394 306 329 230

LSD at the 1 level 5324 413 443 311



0

50

100

150

200

250

300

350

400

450


Groups

Con

cent

artio

n (micro

gg

tiss

ue)


a b a ad

b

c

a

dc b a

db c

a

Results

٨٩



17)















kidney and testis

Results

٩٠


Tissues Groups

Liver





4097plusmn1488c

-1812 41419plusmn49b

-158 3731plusmn1314a


4846plusmn107a 15 89

53465plusmn196b 686

42807plusmn663ab

171 33184plusmn901b


4771plusmn168b 1410

66878plusmn369a 3366

445012plusmn84a 574

37674plusmn1703a


LSD at the 5 level 3737 6783 1908 3485

LSD at the 1 level 5041 9151 2575 4702



0

100

200

300

400

500

600

700

800


Groups

Con

cent

ratio

n (micro

gg

tissu

e)


c bca ab

b

c

b

a

b b ab a

aba

ba

Results

٩١














experiment

Results

٩٢


Tissues Groups

Liver



115plusmn0046b -1353


132plusmn0065a -075


134 plusmn 0021a 075






0

02

04

06

08

1

12

14

16


Groups

Con

cnet

ratio

n (micro

gg

tiss

ue)

Liver

a

b

a a

Results

٩٣


except Se (ngg)


vulgare plants




Element




Discussion

٩٤

























Discussion

٩٥



























1993)

Discussion

٩٦


















2003)










Discussion

٩٧



Missiry et al 1998)

























Discussion

٩٨














the liver













Discussion

٩٩



























Discussion

١٠٠



























Discussion

١٠١




























Discussion

١٠٢


























Discussion

١٠٣



























Discussion

١٠٤









al 2007)


















Discussion

١٠٥






















peroxidation






Discussion

١٠٦



























Discussion

١٠٧













1990)















Discussion

١٠٨



























Discussion

١٠٩




























Discussion

١١٠



















damage








Discussion

١١١












Tatar 1987)





6173 Iron











Discussion

١١٢





























Discussion

١١٣







Gores 1995)





















Discussion

١١٤





























Discussion

١١٥















6176 Manganese














Discussion

١١٦



























Discussion

١١٧



(Tanaka et al 1988)

























Discussion

١١٨




























Discussion

١١٩





























Discussion

١٢٠























and Hwang 2004)




Discussion

١٢١


rat testis















and Naidoo 1995)







(Sorenson 2002)



Discussion

١٢٢






























Discussion

١٢٣

















Discussion

١٢٤

Discussion

١٢٥

Gmaha15doc

124














estimated










Gmaha15doc

125



















control rats




References

١٢٦







17(1) 183-194



Res Technol 212(5) 551-560








Egypt










References

١٢٧











41(7) 926ndash33











71(10) 1397-421








References

١٢٨







Chem 20(4) 470-475





London 2 260









Associat 129(5) 617-620








References

١٢٩



























Res Commum 94(4) 1296-1302

References

١٣٠



159



561-586




Rad Res 159(4) 47-83













207





References

١٣١



882-8



























References

١٣٢




6(2) 111-120





235










Lipid Res 30 1895-1906







Biol Chem 273(9) 5279-87



References

١٣٣



Ther 47(1) 117-136




198




1009-1017


















References

١٣٤


Acta 1001(3) 316-324















Int 47(6) 1019-1027








Med 31(6) 907-917




References

١٣٥








J Androl 4(6) 387-92




328(2) 87-94





annu Conf 1st p-5










16575

References

١٣٦







42(6)1189-94












Nutr 128(5)825-831










References

١٣٧












90




Anim Sci 33(2) 75- 83












References

١٣٨



120



























References

١٣٩



115 85-107











133






Rad Res 37 (5) 1261-1273








References

١٤٠






Elem Res 68(1-2) 25-30














345




Rad Res 45(4) 543-8




References

١٤١


















Food Chem 56(6) 1912-20




Commun 3(5) 257-72







References

١٤٢
















Radiol 59 597-602








2080






References

١٤٣





Gastroenterol 57










J Vet Med 8(4)227-232















References

١٤٤






Surg Res 74(2) 149-154









s112








FEBS lett 281(1-2) 9-19




86



References

١٤٥



Physiol 160(1)1-8



31-8



156-81










7(2)181






Bulletin 37 2016-2021





References

١٤٦







Chem 256(23) 12322-28





Vasc Biol 22(9) 1402-1408




365 (2) 333-342











(CSIR) New Delhi 83

References

١٤٧



No 197 379







Biol 10 62-76



28(1) 163-186
















References

١٤٨


288-93













40(2) 74ndash81



77(7) 780- 794








Biophys 405(2) 170-177



References

١٤٩





13(2)17-25






333




Sci Appli 18(2) 367-384








Biochem 27(23) 8509-8515



671-701



References

١٥٠


Brain Res 606(1) 106-10





97





Chem 42 64- 69



54(2) 481-9















References

١٥١




Sci 60(11) 1125-30

















Rinsho 54(1) 46-51




3381




337-49

References

١٥٢



634-40



Res 119(2) 356-65





70-3






13(3)401-9




60(1-2)139-144



Radic Res 29(2) 93-101




Photomed 8(6) 232-5

References

١٥٣











92(7) 2632-9






843-6













References

١٥٤


667




Biochem 6 577- 581




















86-95



Physiol 166(2) 384-386

References

١٥٥



630-644



43-47






Pharmacol 127(5) 1159-1164






Med 98(4) 463-81



Shams Univ








References

١٥٦





Med 4 2





385ndash391









pp 1



18(1) 162-166






References

١٥٧



Res 111(2) 267-275












105-121








Fed Proc 29(4) 1482-8





References

١٥٨



562(1-3) 129-133










435- 44




Bioch 6 263-268











121(1) 31-8

References

١٥٩




Res 143 316-319




Academy Press



514







Applic 21(2) 515-530




23(2) 153-160


England Wiley 4






References

١٦٠








Sci 22(1) 30-5






Applic 18(2) 335-349




Applic 18(2) 227-293










References

١٦١









New York I 247-285




















7(2) 261-76

References

١٦٢



17(2) 281-295




27(A) 43-55


















52(7) 1890-7





References

١٦٣










51(3) 283-97










62









References

١٦٤






45








Chem 15(2) 997-1003







447-54




91





References

١٦٥






819






30(4) 725-38











USA 33-40




1229-34

References

١٦٦









252-75




















Appplic 2 107-124

References

١٦٧




Exp Biol Med 202(3) 295-301







Zool 28(A) 191-9






Applic 19(2) 433-452








12(4) 251ndash259





References

١٦٨



101-9




82














707-13








References

١٦٩














115-128











306-15




1640-9

References

١٧٠







54(4) 733-6






















6

References

١٧١













31(3) 257-236












Toxicol 46(12) 3842-3850





References

١٧٢


























437-568



References

١٧٣



Chem 9(6) 639-662








78

















References

١٧٤



77-86









659-65













9(1) 23-27




Biol 364(5) 1084-1102

References

١٧٥




Res 32(2) 293-308



320



59(Suppl 5) 401-12



Inst 97 125







Shi 54(8) 1409-1414










References

١٧٦


Applic 19 499-512









Chem 37(17) 2637-2654











17(5) 546-8







References

١٧٧










181-8


Mol Med 6(6) 607-612
















1 753

References

١٧٨









89(2-3) 145ndash154







6(1-2) 681- 688




76(6) 757-762






radiation research




References

١٧٩











Biochem 110(2) 169-173







Biol Chem 284(13) 4793-6



189(1-2) 1-20







References

١٨٠








Ann Arbor














273



In Oil Chem 2 1-14



43(1) 27-32

References

١٨١



Food Chem 42(3) 629-632







Gynecol 135(3) 372-6







Applic 17(1) 47-60










5170



References

١٨٢



Inflamm 2006(5) 1-9





المختلفة




























جاما









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2010

by maha mahmoud ali mohammed · 2012. 8. 17. · maha mahmoud ali mohammed b.sc. zoology and...

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