therapeutic role of cuminum cyminum on ethanol and thermally oxidized sunflower oil induced toxicity

8/8/2019 Therapeutic role of cuminum cyminum on ethanol and thermally oxidized sunflower oil induced toxicity

1/6

416 K. ARUNA ET AL.

Copyright 2005 John Wiley & Sons, Ltd. Phytother. Res . 19, 416421 (2005)

Copyright 2005 John Wiley & Sons, Ltd.

PHYTOTHERAPY RESEARCHPhytother. Res. 19, 416421 (2005)Published online in Wiley InterScience (www.interscience.wiley.com). DOI : 10.1002/ptr.1596

Received 27 January 2004 Accepted 27 August 2004

* Correspondence to: Dr V. P. Menon, Department of Biochemistry,Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.E-mail: [email protected]

Therapeutic Role of Cuminum cyminum onEthanol and Thermally Oxidized Sunower oilInduced Toxicity

K. Aruna, R. Rukkumani, P. Suresh Varma and Venugopal P. Menon*Department of Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India

Ethanol is one of the most widely used and abused drugs, increasing lipid levels in humans and experimentalanimals. Heating of oil rich in polyunsaturated fatty acids (PUFA) produces various lipid peroxidative endproducts that can aggravate the pathological changes produced by ethanol. In the present communication, theeffect of Cuminum cyminum was investigated on alcohol and thermally oxidized oil induced hyperlipidaemia.The results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) andgamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipidsin the plasma of rats given alcohol, thermally oxidized oil and alcohol +++++ thermally oxidized oil when comparedwith the normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides wereincreased signicantly in rats groups given alcohol, thermally oxidized oil and alcohol +++++ thermally oxidized oilwhen compared with the normal control rats. The levels were decreased when cumin was given along withalcohol and thermally oxidized oil. The level of phospholipids decreased signicantly in the liver and kidneyof groups given alcohol, thermally oxidized oil and alcohol +++++ thermally oridized oil when compared with thenormal control rats. The level increased when cumin was administered along with alcohol and thermallyoxidized oil. The activity of phospholipase A and C increased signicantly in the liver of groups given alcohol,thermally oxidized oil and alcohol +++++ thermally oxidized oil when compared with the normal control rats,whereas the activity was decreased with the cumin treatment. The results obtained indicate that cumin candecrease the lipid levels in alcohol and thermally oxidized oil induced hepatotoxicity. Copyright 2005 JohnWiley & Sons, Ltd.

Keywords: ethanol; hepatotoxicity; Cuminum cyminum ; spices; thermally oxidized sunower oil; PUFA; phospholipases.

when the fat is used repeatedly, oxidative and thermaleffects result in the formation of many volatile andnon-volatile products, some of which are potentiallytoxic (Alexander, 1981). Ingestion of the decompositionproducts formed as a result of thermal abuse andoxidation of frying oils is known to lead to a varietyof diseases (Twex et al. , 1998).

Ayurveda is an ancient form of Indian medicine,which deals with plants and plant products. This indi-genous form of medicine uses the active ingredientspresent in plants to treat diseases (Ravikumar and

Anuradha, 1999). Plants are frequently considered tobe less toxic and more free from side effects than syn-thetic ones (Valiathan, 1998). Spices are well knownappetizers and are considered essential in culinaryart all over the world. India is known as the home of spices and is an important exporter of this commodity.Besides their extensive use in food preparation tolend variety, they are also used in the traditional systemof medicine in the treatment of many ailments. Cuminis widely used in Ayurvedic medicine for the treat-ment of dyspepsia, diarrhoea and jaundice. It also hasdiuretic, carminative, emmanogogic, antispasmodic andanticarcinogenic properties (Joshi, 2000). The presentwork was undertaken because very little or no work

has been done to study the effect of cumin on lipidlevels in alcohol and thermally oxidized oil inducedtoxicity.

INTRODUCTION

Ethanol is a powerful inducer of hyperlipidaemia inhumans and animals (Avagaro and Cazzlolatu, 1975). Itoccurs when the intracellular redox potential and redoxsensitive nutrient metabolisms are disturbed by alcohol(Lieber and Davidson, 1962). An excessive accumula-tion of reducing equivalents favours hepatic lipogenesis,decreases the hepatic release of lipoproteins, increasesthe mobilization of peripheral fat, enhances the uptake

of circulating lipids and decreases the fatty acid oxida-tion and thus increases the retention of lipids in theliver (Rukkumani et al. , 2002).

The earlier concept of PUFA in disease preventionhas undergone a change. In contrast to earlier ndingsshowing a reduced risk of coronary heart diseases dueto PUFA intake (Nordey and Goodnight, 1990), cur-rent data on dietary fat suggest that it is not just thepresence of PUFA but the type of PUFA that is im-portant. A high PUFA n-6 content and n-6/n-3 ratioin dietary fat is considered to be atherogenic (Sircarand Kansra, 1998). Moreover heating of oil producesvarious peroxidative changes. During deep fat frying


2/6

CUMIN ON ETHANOL TOXICITY 417


MATERIALS AND METHODS

Experimental animals. Male albino rats Wistar strain(body weight 140160 g) bred in the Central AnimalHouse, Rajah Muthiah Medical College, were used inthis study. The animals were housed in plastic cageswith lter tops under seminatural light-dark conditionsand at room temperature. The animals were fed onpellet diet (Hindustan Lever Limited, Mumbai) andwater was given ad libitum .

Chemicals. Ethanol was purchased from E. Merck,Darmstadt, Germany. Sunower oil (Gold winner) waspurchased from the local market, Chidambaram, SouthIndia. Oil was subjected to two frying cycles of 30 mineach at 180 C to produce thermally oxidized oil. Allother chemicals and biochemicals used for the experi-ments were of analytical grade.

Plant material. Cumin seeds were purchased from thelocal market, Chidambaram, Tamil Nadu, India. Theseed was identied by a botanist in the Departmentof Botany, Annamalai University. Seeds were cleanedof extrageneous matter, dried in shade and nelypowdered in a mechanical mixer. The cumin powderwas suspended in water just before use.

Experimental design. The animals were randomized intothe following groups.

Group 1: Normal control rats given standard pellet diet.Group 2: Rats given 20% ethanol 5 mL each equival-

ent to (7.9 g ethanol/kg body weight) dailyusing an intragastric tube (Rajakrishnan et al. ,1997).

Group 3: Control rats given cumin (0.25 g/kg bodyweight) in distilled water using an intragastrictube (Surya et al. , 2002).

Group 4: Rats given thermally oxidized sunower oil(15%) + cumin (0.25 g/kg body weight).

Group 5: Rats given 20% ethanol + cumin (0.25 g/kgbody weight).

Group 6: Rats given 20% ethanol + thermally oxidizedsunower oil (15%) + cumin (0.25 g/kg bodyweight).

Group 7: Rats given thermally oxidized sunower oil(15%).

Group 8: Rats given thermally oxidized sunower oil

(15%)+

20% ethanol.

At the end of the experimental period (45 days) therats were given anaesthesia (ketamine hydrochloride,30 mg/kg body weight) and were killed after an over-night fast by decapitation. Blood was collected inheparinized tubes and the plasma was separated forvarious estimations. Tissues (liver and kidney) wereremoved, cleared of blood and collected in ice coldcontainers containing 0.9% NaCl for various estima-tions. The project was approved by the institutionalethics committee.

Biochemical estimations. The activity of plasma gammaglutamyl transferase (E.C. 2.3.2.2) was assayed by themethod of Fiala et al. (1972). The activity of plasmaaspartate transaminase (E.C. 2.6.1.1) was assayed bythe method of Reitman and Frankel (1957) and alka-line phosphatase (E.C. 3.1.3.1) by the method of Kingand Armstrong (1988) using reagent kits, Tissue lipidswere extracted according to the method of Folch et al.(1957). Plasma and tissue cholesterol was estimatedusing a reagent kit (Allain et al. , 1974). Triglycerideswere estimated by the method of Foster and Dunn(1973) and phospholipids by the method of Zilversmitand Davis (1950). Phospholipase A (E.C. 3.1.4.1) wasassayed by the method of Rimon and Shapiro (1959)and phospholipase C by the method of Kleiman andLands (1969).

Statistical analysis. Statistical analysis was carriedout using analysis of variance (ANOVA) followed byDuncans multiple range test (DMRT). The level of statistical signicance was set at p < 0.05.

RESULTS

Table 1 shows changes in the body weight of differentgroups. The average weight gain in rats given alcohol,thermally oxidized oil and alcohol + thermally oxidizedoil was signicantly reduced when compared with thenormal control rats. The animals showed near a normalpattern of weight gain when cumin was given alongwith thermally oxidized oil and alcohol.

The change in the activities of plasma AST, ALPand GGT are given in Table 2. The activity of AST,ALP and GGT was increased in alcohol, thermallyoxidized oil and alcohol + thermally oxidized oil fedgroups when compared with the normal control group.

Administration of cumin along with thermally oxidized

Table 1. Change in body weight

Group Initial body weight (g) Final body weight (g) Change in body weight (g)

1. Control 137.20 6.13 213.30 7.51 76.01 6.73 acdef

2. Alcohol 150.26 5.29 202.92 4.73 52.66 3.98 b

3. Cumin 148.79 3.78 224.46 5.23 75.67 2.54 cdef

4. Thermally oxidized oil + cumin 139.83 4.61 215.15 3.79 73.88 5.93 defg

5. Alcohol + cumin 141.27 2.39 211.69 6.25 70.42 4.53 efgh

6. Alcohol + thermally oxidized oil + cumin 145.71 5.62 215.69 2.79 69.90 4.51 fg

7. Thermally oxidized oil 140.37 4.39 205.54 8.39 65.17 3.41 gh

8. Alcohol + thermally oxidized oil 151.23 3.27 211.46 7.43 60.23 5.28 h

Values are mean SD from six rats in each group.Values not sharing a common superscript differ signicantly at p < 0.05 (DMRT).


3/6

418 K. ARUNA ET AL.


Table 2. Change in the activity of AST, ALP and GGT

Group AST (IU/L) ALP (IU/L) GGT (IU/L)

1. Control 83.95 4.19 acde 79.20 4.87 acdef 0.605 0.04 acdef

2. Alcohol 140.26 8.20 b 147.09 7.73 b 1.251 0.13 b

3. Cumin 84.91 4.98 cde 77.34 4.23 cde 0.600 0.05 cdef

4. Thermally oxidized oil + cumin 88.50 2.13 def 83.00 1.98 def 0.613 0.02 def

5. Alcohol + cumin 92.92 5.45 ef 83.16 5.17 ef 0.620 0.04 ef

6. Alcohol + thermally oxidized oil + cumin 95.90 5.65 f 85.35 5.16 f 0.645 0.06 f

7. Thermally oxidized oil 120.81 5.64 g 123.72 8.71 g 0.789 0.05 g

8. Alcohol + thermally oxidized oil 181.45 13.07 h 171.89 10.35 h 1.415 0.07 h


Table 3. Change in the level of plasma cholesterol, triglycerides and phospholipids

Group Cholesterol (mg/dL) Triglycerides (mg/dL) Phospholipids (mg/dL)

1. Control 97.40 5.04 acde 77.14 3.10 acdef 90.77 5.05 acde

2. Alcohol 138.99 6.84 b 106.41 5.60 b 130.40 6.35 bg

3. Cumin 99.89 4.21 cdef 75.35 4.79 cdef 90.48 4.13 cde

4. Thermally oxidized oil + cumin 101.92 5.64def

79.92 1.78def

93.48 4.13de

5. Alcohol + Cumin 102.11 5.02 ef 80.70 3.07 ef 97.30 5.16 ef

6. Alcohol + thermally oxidized oil + cumin 105.62 6.66 f 81.35 5.72 f 101.01 6.78 f

7. Thermally oxidized oil 130.27 5.89 g 98.29 4.13 g 125.29 3.75 g

8. Alcohol + thermally oxidized oil 150.17 2.39 h 139.07 7.54 h 153.29 7.34 h


oil and alcohol markedly reduced the activities of theseenzymes.

Table 3 includes changes in the level of plasma cho-lesterol, triglycerides and phospholipids. The levels wereincreased signicantly in the alcohol, thermally oxidizedoil and alcohol + thermally oxidized oil fed groups whencompared with the normal control group. The level wasdecreased when cumin was administered along withthermally oxidized oil and alcohol.

The change in the levels of tissue cholesterol, trigly-cerides and phospholipids are given in Table 4. Thelevels of cholesterol and triglycerides were increasedsignicantly in the liver and kidney of alcohol, ther-mally oxidized oil and alcohol + thermally oxidized oilgiven groups when compared with the normal controlgroup but decreased after cumin treatment. The levelof phospholipids decreased signicantly in alcohol, ther-mally oxidized oil and alcohol + thermally oxidized oilgiven groups when compared with the normal control

group. The level was increased on administration of cumin to the above groups.Table 5 gives the changes in the activity of phospho-

lipase A and C. Alcohol and thermally oxidized oiladministration signicantly increased the activity of phospholipase A and C in the liver when comparedwith the normal control group. The administration of cumin to thermally oxidized oil, alcohol and alcohol +thermally oxidized oil fed rats resulted in a markedreduction in the activities of these enzymes.

DISCUSSION

Alcohol is a toxic substance when consumed inexcess and results in a variety of pathological con-

ditions. In our study, the average weight gain by ratsduring the experimental period was signicantly reducedin the alcohol, thermally oxidized oil and alcohol +thermally oxidized oil fed rats when compared withthe normal control rats. Previous studies have alsoshown a decrease in weight gain on alcohol treatment(Rajakrishnan et al. , 1996). Alcohol is known to reducethe absorbance of foodstuff and nutrients (Mendenhallet al. , 1969), which may be the cause of the decrease inthe weight gain observed in our study. A better weightgain in the cumin fed groups demonstrates the pro-tective effect of cumin.

Damage to the liver after ethanol ingestion is a wellknown phenomenon and the obvious sign of hepaticinjury is the leakage of cellular enzymes into the plasma(Baldi et al. , 1993). Increased activity was observed of plasma GGT, AST and ALP in alcohol, thermally oxi-dized oil and alcohol + thermally oxidized oil treatedrats. Previous reports have shown that exposure of

hepatocytes to ethanol perturbs the membrane struc-ture and functions thereby increasing the leakage of AST (Rajakrishnan and Menon, 2001). Ethanol causesstructural and functional changes in the mitochondriaand increases membrane permeability leading to a leak-age of mitochondrial enzymes into the circulation (Deviet al. , 1993). Serum GGT is widely used as a laboratorytest for hepatobiliary diseases in particular, for alco-holic liver disease and for alcohol induced liver dam-age (Nakanishi et al. , 2000). It has been found thatsusceptibility to alcohol may be related to the consump-tion of different types of dietary fat (Nanji and French,1986). Ethanol induction of CYP 450 2E1 was found tobe related to the concentration of polyunsaturated fatty

acids (PUFA) in the diet (Amet et al. , 1998). The in-creased activity of AST, ALP and GGT in thermallyoxidized oil and alcohol + thermally oxidized oil fed


4/6



groups may be due to increased volatile and other non-toxic agents, which are produced during the thermaloxidation of oil. Previous reports have also shown(Hageman et al. , 1991; Shibayama et al. , 1991) increasedactivity of plasma AST and ALP in rats fed thermallyoxidized oil. The observed decrease in the activity of hepatic marker enzymes after cumin administrationshows that cumin preserves the structural integrity of the liver from the toxic effects of alcohol and thermallyoxidized oil.

Marked alterations in lipid metabolism werereported in chronic ethanol feeding (Day et al. , 1993).Our results show increased levels of cholesterol andtriglycerides in the plasma, liver and kidney of ther-mally oxidized oil, alcohol and thermally oxidized oil +alcohol fed groups when compared with the normalcontrol group. Alcohol feeding is known to increasethe biosynthesis and decrease the catabolism of bothfatty acids and cholesterol, resulting in their accumula-tion in the liver and causing hyperlipidaemia (Josephet al. , 1991). The increased cholesterol may be due toincreased -hydroxy-methyl-glutaryl CoA (HMG Co A)reductase activity by ethanol, which is the rate limitingstep in cholesterol biosynthesis (Ashakumari andVijayammal, 1993). The microsomal induction result-ing from long term alcohol consumption not only ac-celerates the oxidation of ethanol but also increasesthe synthesis of triacylglycerols (Savolainen et al. , 1984).Previous studies have shown that diets rich in PUFAstimulate the production of chylomicrons by the intes-tine (Hocquette and Bauchart, 1999), which may be thereason for the increased level of cholesterol in ther-mally oxidized oil and alcohol + thermally oxidized oilfed groups. It has also been reported that ingestion of oxidized lipids rich in linoleic acid cause profoundalterations in membrane composition, uidity and func-tion. These alterations are likely to be associated withan enhanced cholesterol turnover, as indicated by thegreater cholesterol excretion observed in the experi-mental rats (Hochgraf et al. , 1997). The increasedtriglyceride levels after oil ingestion may be due to theincreased availability of substrate FFA for estericationand increased production of chylomicrons in the intes-tine. The level of cholesterol and triglycerides was foundto be decreased when cumin was administered alongwith thermally oxidized oil and alcohol fed rats. De-creased cholesterol levels may be due to decreasedabsorption from the intestine and decreased syn-thesis or increased catabolism. The decreased levels of

triglycerides may be due to decreased free fatty acidsynthesis, increased utilization or decreased glycerolformation.

Phospholipids, the backbone of cellular membranes,are the primary targets of peroxidation and can be al-tered by ethanol (Yamada et al. , 1985). Our results showincreased levels of phospholipids in the plasma anddecreased levels in the liver, kidney of alcohol, ther-mally oxidized oil and alcohol + thermally oxidized oilfed groups when compared with the normal controlgroup. The decreased concentration of phospholipidsin the tissues indicates accelerated phospholipid degra-dation (Choy et al. , 1980) and can result in the modi-cation of the composition, structure and stability of

cellular membranes, resulting in membrane dysfunction(Hubbell and MeConnell, 1971). In this context, Jayaet al. (1994) reported a decrease in the phospholipidT

able4.Changes in theleveloftissuecholesterol,triglycerides and phospholipids

Cholesterol(mg/100gtissue)

Triglycerides (mg/100gtissue)

Phospholipids (mg/100gtissue)

Group

Liver

Kidney

Liver

Kidney

Liver

Kidney

1.Control

352.99 16.12 a

c d e

326.80

19.29 a

c d e

395.04 15.66 a

c d e

513.50

17.31 a

c d e

1832.04 75.11 a

c d e

f

1445.87 97.30 a

c d e

f

2.Alco

hol

564.60 24.05 b

527.81

28.29 b

535.10 28.49 b

652.34

35.64 b

1646.38 71.41 b

1264.02 62.87 b

3.Cum

in

387.27 20.95 c

d e

f

321.63

20.01 c

d e

389.16 23.43 c

d e

509.09

23.29 c

d e

1817.36 90.49 c

d e

f

1450.39 83.48 c

d e

f

4.Thermally oxidizedoil

+ cumin

373.72 11.95 d

e f

340.73

11.29 d

e f

409.21 26.34 d

e f

525.68

23.02 d

e f

1797.11 85.64 d

e f

1432.56 71.74 d

e f

5.Alco

hol

+ cumin

392.60 19.30 e

f

345.18

19.60 e

f

413.21 29.32 e

f

536.91

33.54 e

f

1781.33 63.28 e

f

1415.17 56.50 e

f

6.Alco

hol

+ thermally oxidizedoil

+ cumin

422.96 24.66 f

356.34

20.24 f

429.81 26.12 f

548.64

36.96 f

1758.52 57.32 f

1394.15 69.41 f

7.Thermally oxidizedoil

470.39 35.21 g

459.71

26.75 g

451.07 20.07 g

594.29

27.37 g

1697.05 67.11 g

1307.68 81.37 g

8.Alco

hol

+ thermally oxidizedoil

681.71 47.05 h

675.39

37.02 h

759.95 39.20 h

895.68

37.29 h

1401.71 83.98 h

1104.67 87.29 h

Values are mean

SD from six rats ineachgroup.

Values notsharinga commonsuperscriptdiffer signicantly at

p < 0.05 (DMRT).


5/6

420 K. ARUNA ET AL.


Table 5. Change in the activity of phospholipase A and phospholipase C

Phospholipase A (mEq Phospholipase C (mmolesof ester hydrolysed/min/mg of phosphorylcholine

Group protein) formed/min/mg protein

1. Control 0.028 0.002 acdef 0.665 0.05 acdef

2. Alcohol 0.075 0.006 b 0.910 0.07 b

3. Cumin 0.027 0.001 cdef 0.661 0.05 cdef

4. Thermally oxidized oil cumin 0.031 0.02 def 0.675 0.02 def

5. Alcohol + cumin 0.037 0.003 ef 0.685 0.04 ef

6. Alcohol + thermally oxidized oil + cumin 0.041 0.001 f 0.702 0.05 f

7. Thermally oxidized oil 0.067 0.03 g 0.814 0.05 g

8. Alcohol + thermally oxidized oil 0.135 0.07 h 1.124 0.09 h


content of liver and kidney of alcohol fed rats. Cuminadministration along with thermally oxidized oil andalcohol reduced the levels to near normal. This effect

of cumin may be by (i) decreasing the toxicity of ethanoland its metabolic product acetaldehyde, (ii) decreasingthe toxicity of thermally oxidized PUFA and its toxicmetabolites and free radicals.

Intracellular phospholipase A is a diverse group of enzymes with a growing number of members. Theseenzymes hydrolyse membrane phospholipids into fattyacid and lysophospholipid (Basavarajappa et al. , 1998).Lysophospholipids generated by the action of pho-spholipase A can be further metabolized to potentinammatory mediators, such as eicosanoids and platelet-activating factors (Farooqui et al. , 1999). PhospholipaseC attacks the ester bond in position 3, liberating 1,2-diacylglycerol and a phosphoryl base. Our results

showed increased activity of phospholipase A and C inalcohol, thermally oxidized oil and alcohol + thermally

oxidized oil treated rats when compared with the normalcontrol rats. In this context, Zheng et al . (1996) foundthat chronic exposure to ethanol leads to a progres-

sive increase in membrane phospholipase A 2 activity.Ethanol ingestion also induces an increase in microsomalphospholipase C that correlates with an increase in themicrosomal CYP 2E1 and a decrease in microsomal20:4 (arachidonic acid). These changes are associatedwith ethanol induced liver pathology (Nanji et al. , 1993).Earlier studies (Aruna et al. , 2002) also showedincreased activity of phospholipase A and C in the liverof ethanol and thermally oxidized sunower oil +ethanol administered rats. The activity of these enzymeswas decreased in the groups given cumin along withthermally oxidized oil and alcohol showing the protec-tive effect of Cuminum cyminum .

Thus our study shows the protective effect of

Cuminum cyminum on ethanol and thermally oxidizedsunower oil induced toxicity.

REFERENCES

Alexander JC. 1981. Chemical and biological properties relatedto toxicity of heated fats. J Toxicol Environ Health 7 : 125138.

Allain CC, Poon LS, Chan CS, Richmond W, Fu FC. 1974.Enzymatic determination of total serum cholesterol. ClinChem 20 : 470475.

Amet Y, Adas F, Nanji AA. 1998. Fatty acid omega and (omega-1)-hydroxylation in experimental alcoholic liver disease;relationship to different dietary fatty acids. Alc Clin Exp Res 22 : 14931500.

Aruna K, Kalpana C, Viswanathan P, Menon VP. 2002. Toxiceffects of sunower oil and ethanol treated rats. Hepatol Res 24 : 125135.

Ashakumari L, Vijayammal PL. 1993. Additive effect of alcoholand nicotine on lipid metabolism in rats. Indian J Exp Biol 31 : 270274.

Avagaro P, Cazzlolatu G. 1975. Changes in the composition andphysiochemical characteristics of serum lipoproteins dur-ing ethanol induced lipemia in alcohol subjects. Metabolism241 : 12311242.

Baldi E, Burra P, Plebani M, Salvagnini M. 1993. Serummalondialdehyde and mitochondrial aspartate aminotran-sferase activity as marker of chronic alcohol intake andalcoholic liver disease. Ital J Gastroenterol 25 : 429432.

Basavarajappa BS, Cooper TB, Hungund BL. 1998. Effect ofchronic ethanol exposure on mouse brain arachidonic acidspecic phospholipase A2. Biochem Pharmacol 55 : 515521.

Choy PC, Man PYK, Chan AC. 1989. Phosphatidylcholinemetabolism in isolated rat heart. Modulation by ethanoland vitamin E. Biochem Biophys Acta 1005 : 225232.

Day CP, James OF, Brown AS, Bennet MK, Flemming IN,Yeraman SJ. 1993. The activity of the metabolic form ofhepatic phosphatidate phosphohydrolase correlates with theseverity of alcoholic fatty liver in human beings. Hepatology 18 : 832838.

Devi BG, Henderson GI, Frosto TA, Sehenker S. 1993. Effect ofethanol on rat fetal hepatocytes. Studies on cell replication,lipid peroxidation and glutathione. Hepatology 18 : 648659.

Farooqui AA, Litsky ML, Farooqui T, Horrocks LA. 1999.Inhibitors of intracellular phospholipase A2 activity; theirneurochemical effects and therapeutical importance forneurological disorders. Brain Res Bull 49 : 139153.

Fiala S, Fiala AE, Dixon B. 1972. Gamma glutamyl transpeptidasein transplantable chemically induced rat hepatomas andspontaneous mouse hepatomas. J Natl Cancer Inst 48 : 13931409.

Folch J, Lees M, Stanely GHS. 1957. A simple method forthe isolation and purication of total lipids from animalstissues. J Biol Chem 226 : 497509.

Foster CS, Dunn O. 1973. Stable reagents for determination ofserum triglycerides by a colorimetric Hantzsch condensa-tion method. Clin Chim Acta 19 : 338340.

Hageman G, Verhagan H, Schutte B, Kleinjang J. 1991. Bio-logical effects of short-term feeding to rats of repeatedlyused deep frying fats in relation to fat mutagen content.J Food Chem Toxicol 29 : 689698.


6/6



Hochgraf E, Mokady S, Cogan U. 1997. Dietary oxidized linoleicacid modies lipid composition of fat liver microsomes andincreases their uidity. J Nutr 127 : 681686.

Hocquette JF, Bauchart D. 1999. Intestinal absorption, bloodtransport and hepatic and muscle metabolism of fatty acidsin pre ruminent and ruminent animals. Reprod Nut Dev 39 :2748.

Hubbell WL, McConnell HM. 1971. Molecular motion spin-labeledphospholipids and membranes. J Am Chem 93 : 314.

Jaya DS, Augustine J, Menon VP. 1994. Protective role of N-acetyl cysteine against alcohol and paracetamol inducedtoxicity. Indian J Clin Biochem 9 : 6471.

Joseph J, Emannel D, Kadam MB, Joseph PK. 1991. Protectiverole of onion against acute alcoholic fatty liver. Indian J Clin Biochem 6 : 2729.

Joshi SG. 2000. Medical Plants: Family Apicaceae , 1st edn. IBHpublishing Co. Pvt. Ltd: Oxford, 3435.

King EJ, Armstrong AR. 1988. Calcium, phosphorus and phosphatase . In Practical Clinical Biochemistry . CBS Pub-lishers: New Delhi, 458.

Kleiman JH, Lands WEH. 1969. Purication of phospholipase Cfrom Bacillus cereus. Biochem Biochem Acta 187 : 477.

Lieber CS, Davidson CS. 1962. Some metabolic effects by ethylalcohol. Am J Med 33 : 319327.

Mendenhall CL, Bradford RH, Furman RH. 1969. Effects ofethanol on glycerolipid metabolism in rat liver. BiochemBiophys Acta 187 : 501509.

Nakanishi N, Nakamura K, Suzuki K, Tatara K. 2000. Lifestyleand the development of increased serum gamma-glutamyltransferase in middle aged Japanese men. Scand J ClinLab Invest 60 : 429438.

Nanji AA, French SW. 1986. Dietary factors and alcoholic cir-rhosis. Alc Clin Exp Res 10 : 271273.

Nanji AA, Lamb RG, Sadrzadeh SMH, Denneberg AJ,Waxman DJ. 1993. Changes in microsomal phospholipaseand arachidonic acid in experimental alcoholic liver injury;relationship to cytochrome P-450 2E1 induction and con-jugated diene formation. Alc Clin Exp Res 17 : 598603.

Nordey A, Goodnight SH. 1990. Dietary lipids and thrombosis,relationships to atherosclerosis: a review. Arteriosclerosis 10 : 149163.

Rajakrishnan V, Menon VP. 2001. Potential role of antioxidantsduring ethanol induced changes in the fatty acid composi-tion and arachidonic acid metabolites in male Wistar rats.Cell Biol Toxicol 17 : 1122.

Rajakrishnan V, Viswanathan P, Menon VP. 1996. Adaptation ofsiblings of female rats given ethanol, effect of N-acetylcysteine. Amino Acids 12 : 323341.

Rajakrishnan V, Viswanathan P, Menon VP. 1997. Hepatotoxiceffect of alcohol on female rats and siblings: Effects of N-acetyl cysteine. Hepatol Res 9 : 3750.

Ravikumar P, Anuradha CV. 1999. Effect of fenugreek seeds onblood lipid peroxidation and antioxidants in diabetic rats.Phytother Res 13 : 197201.

Reitman S, Frankel AS. 1957. A colorimetric method for thedetermination of serum glutamic, oxaloacetic and glutamicpyruvic transaminases. Am J Clin Pathol 28 : 5356.

Rimon A, Shapiro B. 1959. Properties and specicity ofphospholipase A. Biochem J 71 : 620623.

Rukkumani R, Sri Balasubhashini M, Viswanathan P,Menon VP. 2002. Comparative effects of curcumin andphoto-irradiated curcumin on alcohol and polyunsaturatedfatty acid-induced hyperlipidemia. Pharmacol Res 46 : 257264.

Savolainen MJ, Baraona E, Pikkrainen P, Liber CS. 1984.Hepatic triacylglycerol synthesizing activity during progres-sion of alcoholic liver injury in the baboon. J Lipid Res 25 :813820.

Shibayama Y, Asaka S, Nakata K. 1991. Endotoxin hepatotoxicityaugmented by ethanol. Exp Mol Pathol 55 : 196301.

Sircar S, Kansra V. 1998. Choice of cooking oilsmyths andrealities. J Indian Med Assoc 96 : 304307.

Surya D, Vijayakumar RS, Senthilkumar R, Nalini N. 2002.Hypolipidemic effect of Cuminum cyminum L. on alloxan-induced diabetic rats. Pharmacol Res 46 : 251255.

Twex H, Ismail HM, Sumars S. 1998. The effect of intermittentheating on some chemical parameters of rened oils usedin Egypt: a public health nutrition concern. Int J Food Sci Nutr 49 : 339342.

Valiathan MS. 1998. Healing plants. Curr Sci 11 : 75. 11221127.Yamada S, Mark KM, Lieber CS. 1985. Chronic ethanol con-

sumption alters rat liver plasma membrane and potentiatethe release of alkaline phosphatase. Gastroenterology 88 :17991806.

Zheng Z, Barkai AI, Hungund BL. 1996. Effects of ethanol on theincorporation of free fatty acids into cerebral membranephospholipids. Neurochem Int 28 : 551555.

Zilversmit DB, Davis AK. 1950. Microdetermination of plasmaphospholipids by trichloracetic acid precipitation. J Lab ClinMed 35 : 155160.

therapeutic role of cuminum cyminum on ethanol and thermally oxidized sunflower oil induced toxicity

Documents