efficacy of flagymox (amoxicillin and metronidazole

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80

Aboubakr et al World Journal of Pharmacy and Pharmaceutical Sciences

EFFICACY OF FLAGYMOXreg (AMOXICILLIN AND

METRONIDAZOLE COMBINATION) IN CONTROLLING

CLOSTRIDIUM PERFRINGENS INFECTION IN BROILER CHICKENS

Mohamed Aboubakrand Mohamed Elbadawy

Department of Pharmacology Faculty of Veterinary Medicine Benha University Egypt

ABSTRACT

The efficacy of amoxicillin and metronidazole and their combination

(Flagymoxreg) in controlling experimental Clostridium perfringens

infection in broiler chickens were investigated in two hundred and

forty apparently healthy one day old unsexed Hubbard broiler chicks

The chicks were divided into 8 groups and all treatments were orally

administered in drinking water for five consecutive days Group 1

uninfected untreated Group 2 uninfected and treated with therapeutic

doseofamoxicillin(20 mgkg b wt) Group 3 uninfected and treated

with therapeutic dose of metronidazole (40 mgkg bwt) Group 4

uninfected and treated withFlagymoxreg(amoxicillin 10 mgkg b wtplus

metronidazole 20 mgkg b wt) Group 5 infected and untreated Group 6 infected and

treated with therapeutic dose of amoxicillin Group 7 infected broiler chicks and treated with

therapeutic dose of metronidazole Group 8 infected broiler chicks and treated with

therapeutic dose of amoxicillin plus metronidazole (Flagymoxreg) in drinking water for 5

successive days The efficacy of used drugs were determined on the basis of clinical

symptoms mortality rate body weight body weight gain gain percent feed

consumption feed conversion rate and scores ofintestinal lesionsChanges in serum

biochemical parameters were also determined The in vitro MIC of amoxicillin or

metronidazole against Clostridium perfringens were 2 and 1 microgml respectively It could be

concluded that administration amoxicillin and metronidazole combination (Flagymoxreg) is of

a considerable value in medication of Clostridium perfringens infected broiler chickens than

using amoxicillin or metronidazole separately

KEYWORDS Amoxicillin Metronidazole Efficacy Broilers Biochemical

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 6041

Volume 6 Issue 1 80-95 Research Article ISSN 2278 ndash 4357

Article Received on 04 Nov 2016

Revised on 25 Nov 2016

Accepted on 15 Dec 2016

DOI 1020959wjpps20171-8374

Corresponding Author

Dr Mohamed Aboubakr

Department of

Pharmacology Faculty of

Veterinary Medicine

Benha University Egypt


81


1 INTRODUCTION

Gastrointestinal tract of poultry acts as a reservoir for maintenance of pathogens capable of

inducing diseases[1]

Clostridium perfringensis found in gastrointestinal tract of birds where it

is considered a part of normal bacterial flora[2]

Its etiological agent of a wide range of

diseases in humans and animals[3]

It is an anaerobic rodshape spore forming G +ve bacilli[4]

causing necrotic enteritis in poultry[5]

Necrotic enteritis is infectious diseases in broiler

farms[6]

Its one of most economically important enteric diseases in broilers with mortality

rates up to 50[7]

Its characterized by sudden onset of diarrhea and mucosal necrosis[8]

For many years prophylactic use of antibiotic in feed has been primary means of controlling

necrotic enteritis in broiler industry However development of Clostridium perfringens strain

resistance antibiotic has threatened economic stability of broiler industry[9]

Antimicrobial

therapy is an important tool in reducing enormous losses in poultry industry caused by

bacterial infection[10]

Necrotic enteritis can be prevented by use antibiotics[11]

Among these

antimicrobials amoxicillin and metronidazoleAmoxicillin is a one of most effective β lactam

antibiotic[12]

Its widely used in veterinary medicine because of its broad spectrum

antimicrobial activity good absorption and penetration into tissues[13]

Its bactericidal against

bacteria by inhibition of biosynthesis cell wall mucopeptide during bacterial

multiplication[14]

Metronidazole is antimicrobial agent that has effect on most Gr +ve Gr-ve and anaerobic

bacteria It has antiprotozoal properties[15]

Its active against Clostridium perfringens[16]

The

present study was carried out to evaluate efficacy of amoxicillin and metronidazole either

alone or in combination (Flagymoxreg) against experimentally induced necrotic enteritis in

broiler chickens The in vitro MICs of amoxicillin and metronidazole against Clostridium

perfringens were also determined

2 MATERIALS AND METHODS

21 Drugs

211Amoxicillin

Amoxicillin is semisynthetic broad spectrum penicillin derived from the

basicpenicillinnucleus 6-aminopenicillanic acidIt was used in a therapeutic dose of 20 mgkg

bwt once daily for 5 consecutive days orally or intramuscularly[17]

Amoxicillin

trihydratewas obtained as a pure powder from Sigma Aldrich Chemical Co St Louis USA


82


212 Metronidazole

Metronidazole benzoate is a white powder synthetic antiprotozoal and antibacterial agent

used in oral suspension formulations Its recommended therapeutic dose is 40 mgkg bwt

orally[18]

It was obtained as a pure powder from Sigma Aldrich Chemical Co St Louis

USA

213 Falgymoxreg

Falgymoxreg is a combined antibacterial product containing amoxicillin and metronidazole

Each 100 gm contains Metronidazole 20 gm and Amoxicillin trihydrate 11477 gm (eq to 10

gm Amoxicillin base) It is used as a therapeutic dose of 10 mg amoxicillin plus 20 mg

metronidazolekg bwt It is manufactured by (ATCO Pharma Trading Co) Egypt

22 Experimental chicks

Two hundred and forty apparently healthy one day old unsexed Hubbard broiler chicks

(obtained from El-Kahera poultry Company Egypt) were used in the current study The

chicks were allocated into 8 separated groups 30 birds for each The chicks were floor reared

in separate units under hygienic measures at the chick level They initially had an

environmental temperature of 32degC which reduced 2degC each week A continuous lightening

pattern was used feed and water were provided ad-libitum Chicks were fed on balanced

commercial ration free from any medications obtained from Cairo Poultry Company On the

7th day of age all chicks were vaccinated by HitchnerBl vaccine to protect the chicks against

New Castle disease and on the 14th days of age all chicks were vaccinated against Gumboro

disease The study was carried out for 4 weeks

23 Experimental infection

Clostridium preferenceswas obtained from Animal Health Research Institute Dokki Giza

Egypt At 21stday of age infection was carried out by oral administration of 3 inoculations

each of 2 ml freshly prepared and 24 h incubated thioglycolate broth culture of Clostridium

perferenges (15 x 109 organismsml) on alternate days according to

[19]

The efficacy was assessed by observing clinical symptoms mortality rate body weight gain

gain percent and feed consumption Also by determination of some changes in serum

biochemical parameters ofmedicated chicks


83


24 Experimental design

The total number of (240) oneday old broiler chicks were classified into 8 groups each of 30

chicks Four groups were left uninfected while the other four were infected At 21stday of age

infectionwas carried out as mentioned above Group 1 uninfected and untreated Group 2

uninfected and treated with 20 mgkg b wtof amoxicillin Group 3 uninfected and treated

with 40 mgkg b wtof metronidazole Group 4 uninfected and treated with Flagymoxreg

(a

combination of 10 mgkg b wt amoxicillin and 20 mgkg b wt metronidazole) Group 5

infected and untreated Group 6 infected and treated with 20 mgkg b wt amoxicillin Group

7 infected and treated with 40 mgkg b wt metronidazole Group 8 infected broiler chicks

and treated with Flagymoxreg All medications were orally administered in drinking water for

five consecutive days

25 Blood samples

Blood samples were taken at the end of 1st 10

th and 20

th days post drug administration (which

corresponds to31 41 and 51th

days of age) Five birds from each group were sacrificed for

collection of blood samples whichleft in a slope position to clot at room temperature Serum

was carefully separated and centrifuged at 1000 rpm for10 minutes Clear serum samples

were transferred carefully in clean dry vials and kept frozen at-20degCuntil its biochemical

analysis

25 Efficacy of the drug

251 Clinical symptoms

The clinical symptoms appeared post closterdial infection was recorded[20]

252 Mortality rate

The number of dead chicks in all groups were recorded and calculated as percentage

253 Body weight body weight gain and gain percent

Chicks of each group were individually marked and weighed just prior to infection and

weighed at 1st 10

th and 20

th day after drug administration The gain in body weight was

calculated for each group by subtracting the body weight between two successive weights

254 Feed consumption and Feed Conversion

Feed consumption and feed conversion were calculated weekly for all groups The feed

conversion was calculated as grams of consumed feed per grams of body gain[21]


84


F-conversion= Feed consumption (g) period

Weight gaint (g) period

255 Score of lesions in infected chickens

Intestinal lesions were graded as follows no gross lesions thin-walled or friable

smallintestine mild necrosis or ulceration moderate patches of necrosis severe

extensivenecrosis as in typical field cases[22]

26 In vitro Minimum inhibitory concentrations (MIC)

The in vitro MIC of amoxacillin or metronidazole against Clostridium perfringens were

determined by the serial dilution method[23]

The antimicrobial was dissolved in sterile

distilled water to obtain different concentrations of 100 50 25 10 5 25 1 05 and 01

microgml as stock solutions to use with Clostridium perferenges (15x109 organismsml) and

incubated at 37oc for 24 h At the end of incubation period the tubes were examined visually

for turbidityThe tubes with no visible growth indicate the MIC points

27 Statistical Analysis

The obtained results were statistically explained by[24]

3 RESULTS

Healthy chicks treated with amoxicillin andor metronidazole either alone or in combination

showing no clinical symptoms throughout the experimental period Experimentally infected

broiler chickens with Clostridium perfringens and untreated displayed clinical signs After

experimental infection of broiler chickens with Clostridium perfringens the first mild clinical

signs were evident approximately 24 to 36 h post infection These signs were loss of appetite

depression drooping wings ruffled feathers diarrhea polydipsia dehydration and

emaciation These clinical signs disappeared under the influence of amoxicillin andor

metronidazole either alone or in combination

The in vitro MIC of amoxicillin or metronidazole against Clostridium perfringens were 2 and

1 microgml respectively

The effect of oral administration of amoxicillin (20 mgkg bwt) andor metronidazole (40

mgkg bwt) either alone or in combination for 5 consecutive days on body weight and body

weight gain in healthy and experimentally infected broiler chicks with Clostridium


85


perfringens was displayed in table (1) Effects on feed consumption and feed conversion rate

wererecorded in table (2)

The effect of oral administration (in drinking water) of amoxicillin (20 mgkg bwt) andor

metronidazole (40 mgkg bwt) either alone or in combination(Flagymoxreg) at a dose of 10 mg

amoxicillin plus 20 mg metronidazolekgbwt for 5 consecutive days on some serum

biochemical parameters in healthy and experimentally infected chickens with Clostridium

perfringenswas recorded in tables (345)Effect of amoxicillin (20 mgkg bwt) andor

metronidazole (40 mgkg bwt) or their combination (Flagymoxreg) given in drinking water for

5 consecutive days on intestinal lesion score () in healthy and experimentally infected

broiler chickens with Clostridium perfringens (n= 5) was recorded in table (6)

Table (1) Effect of amoxicillin (20 mgkg bwt) andor metronidazole (40 mgkg bwt)

given alone or in combination (Flagymoxreg)in drinking water for 5 consecutive days on

body weight (gm) and body weight gain (gm) in healthy and experimentally infected

broiler chickens with Clostridium perfringens at 1st 10

th and 20

th day post

administration (n=5)

Body weight gain (gm) Body weight (gm)

20th

day

post

administration

10th

day

post

administration

1st day

post

administration

20th

day

post

administration

10th

day

post

administration

1st day

post

administration

Initial b

wt(20th

day of age)

8196plusmn151 6668plusmn684 4187plusmn111 24303plusmn215 16107plusmn101 9439plusmn128 5052plusmn119 Group 1


8474plusmn673 7131plusmn835 4466plusmn896 25415plusmn129 16941plusmn120 9810plusmn112 5344plusmn124 Group 3 8517plusmn938 7114plusmn993 4649plusmn135 25486plusmn119 16969plusmn139 9955plusmn148 5303plusmn156 Group 4


8281plusmn131 7101plusmn100 3939plusmn134 24596plusmn163 16315plusmn135 9214plusmn174 5275plusmn165 Group 6 8410plusmn112 6946plusmn141 4140plusmn103 24902plusmn2073 16491plusmn104 9445plusmn653 5305plusmn143 Group 7 8293plusmn128 7042plusmn156 4249plusmn119 24950plusmn229 16657plusmn148 9615plusmn107 5366plusmn180 Group 8

Significant at P lt 005 significant at P lt 001 significant at P lt 0001

compared with healthy control group (non- infected non- treated)

Group 1uninfected untreated Group 2 uninfected amoxicillin treated Group 3 uninfected

metronidazole treated Group 4 uninfected Flagymoxreg treated Group 5 Infected untreated

Group 6 Infected amoxicillin treated Group 7 Infected metronidazole treated Group 8

Infected Flagymoxreg

treated


86


Table(2) Effect of amoxicillin (20 mgkg bwt) andor metronidazole (40 mgkg

bwt)given alone or in combination (Flagymoxreg)in drinking water for 5 consecutive

days on feed consumption (FC) and feed conversion rate (FCR) in healthy and

experimentally infected broiler chickens with Clostridium perfringens at 1st 10

th amp 20

th

day post administration (n= 5)

20th

day

post administration

10th

day

post administration

1st day

post administration Period

Groups FCR FC FCR FC FCR FC

197 160676 196 130944 129 54064 Group 1

195 164405 186 131769 124 56006 Group 2

195 164964 187 133011 125 56515 Group 3

192 163798 186 132739 121 56209 Group 4

198 160884 199 129019 147 52004 Group 5

195 161443 190 132009 139 56014 Group 6

194 161585 190 131461 137 56586 Group 7

194 161605 189 130896 134 57055 Group 8


given alone or in combination (Flagymoxreg)in drinking water for 5 successive days on

serum AST (UL) ALT (UL) and alkaline phosphatase (UL) in healthy and

experimentally infected chickens with Clostridium perfringens at 1st 10

th and 20

th day

post administration (n= 5)

Alkaline phosphatase

(UL) ALT (UL) AST (UL) Period

Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

5305plusmn

153

5340plusmn

149

5403plusmn

117

4893plusmn

138

4827plusmn

139

4758plusmn

126

3049plusmn

093

3104plusmn

078

3026plusmn

064 Group 1

5426plusmn

196

5504plusmn

198

5795plusmn

104

4984plusmn

167

5008plusmn

159

5273plusmn

180

3156plusmn

085

3263plusmn

094

3321plusmn

068 Group 2

5317plusmn

162

5389plusmn

142

5794plusmn

113

5037plusmn

159

5028plusmn

147

5205plusmn

143

3098plusmn

073

3206plusmn

089

3354plusmn

089 Group 3

5373plusmn

185

5398plusmn

126

5787plusmn

104

4904plusmn

134

4969plusmn

115

5196plusmn

104

3105plusmn

099

3113plusmn

037

3350plusmn

085 Group 4

5784plusmn

147

5895plusmn

173

5934plusmn

118

5494plusmn

102

5399plusmn

106

5406plusmn

143

3507plusmn

092

3485plusmn

073

3504plusmn

075 Group 5

5347plusmn

199

5408plusmn

186

5788plusmn

117

4918plusmn

178

5020plusmn

155

5296plusmn

144

3108plusmn

069

3226plusmn

099

3284plusmn

069 Group 6

5311plusmn

175

5412plusmn

176

5799plusmn

113

4905plusmn

194

5047plusmn

194

5247plusmn

137

3073plusmn

053

3159plusmn

083

3365plusmn

057 Group 7

5341plusmn

158

5425plusmn

159

5776plusmn

110

4978plusmn

180

5014plusmn

175

5248plusmn

104

3070plusmn

049

3127plusmn

050

3248plusmn

063 Group 8

Significant at P lt 005 significant at P lt 001



87




serum total protein (mgdl) albumin (mgdl) globulin (mgdl) and AG ratio) in healthy

and experimentally infected chickens with Clostridium perfringens at 1st 10

th and 20

th


AG ratio Globulin (mgdl) Albumin (mgdl) Total protein (mgdl) Period

Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day 1

st day

20th

day

10th

day

1st

day

135plusmn

018

143plusmn

019

123plusmn

015

248plusmn

011 242plusmn

014 264plusmn

016 337plusmn

046 345plusmn

032 326plusmn

018 584plusmn

011

587plusmn

018

590plusmn

012 Group 1

127plusmn

012

144plusmn

014

127plusmn

020

270plusmn

030 253plusmn

032 286plusmn

017 344plusmn

028 363plusmn

049 362plusmn

031 614plusmn

019

616plusmn

024 648plusmn

029 Group 2

127plusmn

016

140plusmn

021

134plusmn

013

264plusmn

025 254plusmn

019 276plusmn

014 339plusmn

036 356plusmn

043 369plusmn

029 600plusmn

028

610plusmn

018

645plusmn

014 Group 3

137plusmn

011

142plusmn

013

138plusmn

020

259plusmn

019 259plusmn

017 261plusmn

018 354plusmn

090 367plusmn

032 359plusmn

023 610plusmn

014

621plusmn

019

620plusmn

018 Group 4

074plusmn 013

075plusmn 014

066plusmn 011

315plusmn 010

310plusmn 006

329plusmn 008

234plusmn 011

232plusmn 031

218plusmn 017

549plusmn 006

542plusmn 007

547plusmn 010

Group 5

128plusmn

016

126plusmn

015

078plusmn

013

255plusmn

016 251plusmn

019 313plusmn

010 327plusmn

039 316plusmn

063 243plusmn

025 549plusmn

015 562plusmn

021 556plusmn

006 Group 6

121plusmn 019

118plusmn 018

078plusmn 012

263plusmn 017

258plusmn 012

318plusmn 014

318plusmn 030

304plusmn 054

247plusmn 022

581plusmn 014

560plusmn 019

565plusmn 008

Group 7

126plusmn

025 119plusmn

021

082plusmn

010

258plusmn

016 261plusmn

019 311plusmn

013 325plusmn

028 313plusmn

039 262plusmn

023 583plusmn

018 574plusmn

026 572plusmn

010 Group 8




88




uric acid (mgdl) and creatinine (mgdl) concentrations in serum healthy and


th and 20

th


Creatinine (mgdl) Uric acid (mgdl) Period

Groups

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

145plusmn

016

148plusmn

018

142plusmn

020

498plusmn

023

508plusmn

039

495plusmn

034 Group 1

155plusmn

019

160plusmn

039

209plusmn

012

502plusmn

021

586plusmn

037

663plusmn

046 Group 2

161plusmn

025

162plusmn

017

198plusmn

010

513plusmn

029

562plusmn

049

650plusmn

039 Group 3

147plusmn

020

159plusmn

021

211plusmn

026

499plusmn

035

518plusmn

023

649plusmn

051 Group 4

226plusmn

018

237plusmn

019

241plusmn

020

689plusmn

047

696plusmn

031

685plusmn

026 Group 5

150plusmn

015

161plusmn

019

197plusmn

012

503plusmn

032

523plusmn

020

608plusmn

025 Group 6

148plusmn

017

154plusmn

010

191plusmn

010

510plusmn

021

532plusmn

017

592plusmn

010 Group 7

153plusmn

020

153plusmn

023

199plusmn

009

511plusmn

019

512plusmn

023

578plusmn

011 Group 8



Table (6) Effect of amoxicillin (20 mgkg bwt) andor metronidazole (40 mgkg bwt) or

their combination (Flagymoxreg)at a dose of (10 mg amoxicillin plus 20 mg

metronidazolekg bwt) given in drinking water for 5 consecutive days on intestinal

lesion score () in healthy and experimentally infected broiler chickens with

Clostridium perfringens (n= 5)

Groups

Thin wall

Mild necrosis

and ulceration

Moderate

necrosis

Severe

necrosis

Healthy 20 0 0 0

Infected and non treated 0 40 40 20

Infected + amoxicillin

(20 mgkg bwt) 40 40 0 0

Infected +metronidazole

(40 mgkg bwt) 40 20 0 0

Infected +Falgymoxreg

(10 mg amoxicillin plus 20

mg metronidazole kg bwt)

40 0 0 0


89


4 DISCUSSION

Treatment of broiler chickens infected with clostridium perfringens using amoxicillin alone

at a dose of 20 mgkgbwt or metronidazole alone at 40 mgkgbwt or in combination

(Flagymoxreg) at doses of 10 mg amoxicillin plus 20 mg metronidazolekgbwt showed

improvement in health status of infected birds as evidenced by disappearance of clinical

signs Amoxicillin was effective in abolishing of development of necrotic enteritis[25-26]

Oral

administration of metronidazolewas effective in treatment Clostridium perferengesinfection

in broiler chickens[27]

Our results revealed that Clostridium perfringens infection in broiler chicks resulted in

mortality rate 3667 A nearly similar (40) mortality rate caused by Clostridium

perfringenswas obtained by[7]

The increase in mortality rate in chickens infected with

Clostridium perfringens may be due to the effect of bacterial toxins[28]

In the current study it

has been shown that Clostridium perfringens infected chickens treated with amoxicillin

reduced mortality rate to 10 meanwhile chickens treated with metronidazole show

mortality 667 but combination (Flagymoxreg)between amoxicillin and metronidazole (with

half of their therapeutic doses) reduced mortality rate to 333 Our results were in

accordance with[29]

who recorded that amoxicillin had decreasedthe mortality rate in broiler

chickens infected with Clostridium perfringens In keeping with these lines[30]

found that

metronidazole exert a good activity against most anaerobic bacteria including Clostridium

perfringens and decreasedthe mortality rate caused by it

Our results revealed asignificant increase in body weight weight gain and improvement in

feed conversion rate when compared with healthy untreated chickens Our results were in

agreement with those recorded by[31]

who stated that healthy chicken received amoxicillin

displayed significant increase in body weight weight gain and decreased feed conversion

rate This result coordinated with that reported by[30]

they denoted that metronidazole induce

significant increase in body weight and weight gain beside significant decrease in feed

conversion rate In the present study it has been shown that broiler experimentally infected

with Clostridium perfringens revealed significant decrease in body weight weight gain and

increase in feed conversion rate all over the experimental period post infection Same

reduction in body weight gain and elevation in feed conversion rate was recorded by[8]

who

mentioned that necrotic enteritis resulted in a 12 reduction in body weight and a 109

increase in feed conversion rate compared with healthy birds Anexplanation for decrease in


90


body weight in chickens infected by Clostridium perfringens was stated by[32]

They found

that clostridial toxins had induced damage in intestinal tissue and liver leading to decrease in

nutrients absorption and metabolism which lead to inferior growth performance of birds

Administration of amoxicillin or metronidazole either alone or in combination

(Flagymoxreg)for treatment of Clostridium perfringens infection resulted in improvement in

body weight weight gain feed consumption and feed conversion rate throughout the

experimental period post treatment when compared with uninfected untreated broiler chicks

This improvement in body weight weight gain feed consumption and feed conversion rate

may be due to the antimicrobial effect of used antibacterials in suppression of Clostridium

perfringens and decreased its intestinal colonization leading to prevention of necrotic

enteritis[33]

Our results were supported by those recorded by[34]

who stated that the infected

broiler chickens by Clostridium perfringensand treated with amoxicillin showed

improvement in body weight gain and feed conversion rate Also metronidazole was

effective against Clostridium perfringens infection and induce significant increase in weight

gain[35]

The present study demonstrated that administration of amoxicillin andor metronidazole

either alone or in combination Flagymoxreg) for 5 consecutive days to healthy chickens

displayed significant increase in activity of aspartate aminotransferase alanine

aminotransferase and alkaline phosphatase at 1st day post administration coupled with

insignificant increase at 10th and 20

th day post administration when compared with healthy

untreated chickens Elevation of liver enzymes activity in chickens received amoxicillin may

be due to its hepatotoxicity[36]

Similar results were reported by[37]

who found that healthy

chicken received metronidazole show a significant increase in activity of liver enzymes

Elevation of liver enzymes post metronidazole administration may be due to liver injury[38]

Broiler chickens experimentally infected with Clostridium perfringens and untreated

displayed asignificant elevation in liver enzymes activity all over the experimental period

post infection when compared with uninfected untreated chickens This elevation in activity

of liver enzymes may be due to pathological changes in liver afterClostridium perfringens

infections[39]

or due to clostridial toxin that induced alterations in cellular permeability allows

escape of liver enzymes into serum[40]

Infected broiler chickens treated with amoxicillin

andor metronidazole either alone or together for 5 consecutive days displayed a significant

elevation in activity of aspartate aminotransferase alanine aminotransferase and alkaline


91


phosphatase at 1stday post treatment and insignificant increase at 10

th and 20

th day post

treatment when compared to healthy untreated broiler chickensThese recorded results were

consistent with those reported by[41]

who mentioned that the improved liver enzymes post

treatment in chicken infected by Clostridium perfringensmay be due to the antimicrobial

effect of the used drugs in suppressing of microorganisms invade to l and retarding its

metabolic activity

In the present study healthy broiler chickens received amoxicillin and metronidazole either

alone or in combination in tested dose displayed insignificant elevation in serum total protein

albumin globulin and AG ratio all over the experimental period post administration when

compared with uninfected untreated broiler chickens The obtained result was supported

by[42]

who found that healthy laboratory animals received amoxicillin showed non-

significantchanges in total protein albumin and globulin Also metronidazole induced

insignificant elevation in serum total protein albumin and globulin[43]

Regarding broiler

chickens infected with Clostridium perfringensand untreated there was significant reduction

in total protein albumin and AG ratio post infection beside significant increase in globulin

allover the experimental period post infection Hypoalbuminemia in our study could be due to

the destructive effect of Clostridium perfringens and its toxins on liver cells producing

albumin[40]

In the present study it was recorded that healthy chickens received amoxicillin and

metronidazole either alone or in combination (Flagymoxreg) revealed a significant elevation in

serum uric acid and creatinine at 1st day post administration and insignificant increase at 10

th

and 20th

day post administration when compared with uninfected untreated broiler chickens

On a similar way our observed results were compatible with that reported by[44]

who reported

that an increase in serum uric acid and creatinine after using szlig-lactamases (cefoperazone) in

human Also in keeping with these lines[28]

found that metronidazole evoked asignificant

increase in serum uric acid and creatinine in healthy broiler chickens Experimental infection

with Clostridium perfringens in broiler chickens displayed a significant increase in uric acid

and creatinine levels allover the experimental period post infection when compared with

uninfected untreated broiler chickens Elevation in uric acid creatinine in infected birds with

Clostridium perfringenscould be attributed to the degenerative changes in kidney tubules

preventing excretion of uric acid and creatinine increasing their levels in serum[45]

Infected

broiler chickens and treated with tested dose of amoxicillin andor metronidazole either alone


92


or in combination for 5 consecutive days elicited a significant increase in serum uric acid and

creatinine at 1st day post administration However at 10

th and 20

th day post treatment induced

an insignificant increase in serum creatinine and shift nearly toward the control levels when

compared with healthy untreated broiler chickens

CONCLUSIONS

In conclusion combinationof amoxicillin (10 mgkg bwt) and metronidazole (20 mgkg b

wt)as in Flagymoxreg

is better than using amoxicillin (20 mgkg bwt) or metronidazole (40

mgkg bwt) separately for treatment of necrotic enteritisin broiler chickens

ACKNOWLEDGMENT

The authors wish to thank Prof Dr Ashraf Elkomy (Department of pharmacology Faculty of

Veterinary Medicine Benha University Egypt) for his advices on manuscript writing Also

we thank Dr Sawsan El-Basuni (Department of Poultry diseases Faculty of Veterinary

Medicine Benha University Egypt for her valuable comments on manuscript

REFERENCES

1 Barbara A Trinh H and Songer J (2008) Clostridium perfringens induce necrotic

enteritis in chicks Vet Microb 126 377ndash382

2 Van Immerseel F Huyghebaert G Haesebrouck F and Ducatelle R (2004)

Clostridium perfringens in poultry An emerging threat for animal and public

health Avian Pathol 33 37ndash49

3 Engstroumlm B Fermeacuter C Lindberg A and Gunnarsson A (2003) Molecular typing of

isolates of Clostridium perfringens from healthy and diseased poultry Vet Microbio l94

225-235

4 Attia A Basma S and Amira S (2013) molecular studies on Clostridium Perfringens

resistant to tetracycline ZagVet J 41(1) 169-175

5 Petit L Gilbert M and Popoff M (1999) Clostridium perfringens Toxinotype and

genotype Trends Microbiol 7 104ndash110

6 Immerseel F (2004) Clostridium perfringens in poultry an emerging threat for animal

and public health Avian Path 33 37ndash49

7 Mc Devit R Broker J Acamovic T and Sparks N (2006) Necrotic enteritis a

continuing challenge for the poultry industry Worldrsquos PoultSci J 62 221ndash247

8 Skinner J Bauer S and Wilson J (2010) An economic analysis of the impact of

subclinical (mild) necrotic enteritis in broiler chickens Avian Dis 54(4) 127ndash1240


93


9 Baumgartner J (2003) Antibiotic susceptibility of bacteria associated with endodontic

abcessesJ Endod Finland 29(1) 44ndash47

10 Gadzinski P and Julian R (1992) Necrotic enteritis in turkeys Avian Diseases 36

792-798

11 Brennan J Moore G Poe S Vessie G Barnum D and Wilson J (2001) Efficacy

of infeed tylosin for the treatment of necrotic enteritis in broiler chickens Poultry

Science 80 1451-1454

12 Palmer G Buswell J and Yeoman G (1976) Amoxycillin new veterinary penicillin

Vet Rec 99 84-85

13 Amin A El-Ansary A and Issa Y (1994) Colorimetric determination of amoxicillin in

pure form and in pharmaceutical preparations Talanta 41(5) 691-694

14 Nagaralli B Seetharamappa J and Melwanki M (2002) Sensitive spectrophotometric

methods for the determination of amoxicillin and piroxicam in pure and pharmaceutical

formulations J Pharm Biomed Anal 29 859-864

15 Bennett P and Brown J (2003)Clinical pharmacology 9th

Ed Churchill livingstone

233

16 Carman R(1994) Clostridial enteropathies of rabbits J Small Exotic Anim Med 2

179-181

17 Brander G Pugh D and Bywater R (1993) Veterinary Applied Pharmacology and

Therapeutic Bailliere Tindall 5th Ed 55-63

18 Cybulski W Larson P and Starmer G (1996) Principles of Veterinary Therapeutic

Longman Singapore Publisher (pte) Ltd

19 Baha EIkemoto T and Mc-Dougald L (1997) Intestinal lesions in chickens infected

with clostridium perfringes and E necatrix Vet Microb 54(413) 301-308

20 Sojk W and Carnaghan R (1961) Escherichia coli infection in poultry Res Vet Sci

2 340ndash352

21 Wagner D Furrow R and Bradley B(1983) Subchronic toxicity of growth promoters

in broiler chickens Veterinary pathology 20 353-359

22 Brennan J Skinner J Barnum DA and Wilson J (2003) The efficacy of

bacitracinmethylene disalicylate when fed in combination with narasin in the

management ofnecrotic enteritis in broiler chickens Poult Sci 82 360-3

23 Brady MS Strobel JR and Katz SE (1988) In-vitro analytical system for

determining the ability of antibiotics at residual levels to select for resistance in bacteria

Journal of the Association of Official Analytical Chemists 71 295ndash298


94


24 Snedecor W and Cochran G (1982) Statistical Methods 8th Ed Ames Iowa State

University

25 Vissiennon T Kroger H Kohler T and Kliche R (2000) Effect of amoxicillin and

ionophore on Clostridium perfringens entero- toxaemia in chickens Berliner Muumln

Tierarz Woch 113 9-14

26 Sasaki Y Yamamoto K and Takahashi T (2001) Tetracycline-resistance genes

of Clostridium spp isolated from cattle affected with malignant edema Vet Microbiol

81(1) 61ndash69

27 Sabina M and Nicodemus M (2014) Clostridium Pathogenic roles industrial uses and

medicinal prospects of natural products as ameliorative agents against pathogenic spp

Jordan J of Biolog Sci 7(2) 81-94

28 Sameh M Nasser A and Gehan Gad (2005) Efficacy of metronidazole clindamycin

and the probiotic in Clostridium perferingens infection in chickens 4th Int Sci Conf

Masoura 1393-1205

29 Gharaibeh S Al Rifai R and Al-Majali A (2010) Molecular typing and antimicrobial

susceptibility of Clostridium perfringens from broiler chickens Anaerobe 16 586-589

30 Craig C and Stitzel R (1994) Modern pharmacology 4th Ed Litt le Brown and

Company Boston

31 Silva R Salvarani R Assis N and Pires F (2009) Antimicrobial susceptibility of

Clostridium perfringens strains isolated from broiler chickens Brazilian J of Microb 40

262-264

32 Lovland A and Kaldhusdal M (1999) Liver lesions seen at slaughter as an indicator of

necrotic enteritis in broiler flocks Immun Med Microb 24 45-51

33 Watkins KL Shryock R Dearth N and Saif Y (1997) In-vitro antimicrobial

susceptibility of Clostridium perfringens from commercial turkey and broiler chicken

origin Veterinary Microbiology 54 195-200

34 Lanckriet A1 Timbermont L De Gussem M and Van Immerseel F (2010) the effect of

commonly used antibiotics in a subclinical necrotic enteritis model Avian Pathol 39(1)

63-68

35 Papich M (2002) Hand Book of Veterinary Drugs Saunders Company Philadelphia

36 Harrison G and Harrison L (1986 ( Clinical avian medicine and surgery WB Saunder

Company Philadelphia London Toronto

37 Williams R Marshall R and Catchpole J (2003) A new method for the experimental

production of necrotic enteritis and its use for studies on relationships between necrotic


95


enteritis coccidiosis and anticoccidial vaccination of chickens Sprin-Verl GmbH 90(1)

432-1955

38 Martelli A Allavena A Robbino L and Brambilla G (1990)Comparative of the

sensitivity of rats hepatocytes to the genotoxic effects of metronidazole Pharmacol

Toxicol 66(5) 329-334

39 Coles E (1986) Veterinary clinicalpathology4th Ed WB Saunders Comp Philadelphia

40 Joan F and Pannal P (1981) Clinical chemistry in diagnosis and treatment 3rd Ed

Liayed- Luke London

41 Bryan C John J Ingrid A Brend S and Robrecht F (1998) Comparison of the

efficacies of three fluoroquinolone one of antimicrobial agents given as continous or

pulsed- water medication against Eschaerichia coli infection in chickens Antimicrobial

Agents and Chem 42(1) 83-87

42 Hassan Seham M (1996) Pharmacological studies on cefoperazone tylosin and their

interaction in laboratory animals Ph D Thesis Pharmacology Presented to Zagazig

University

43 Lau A Lam N Piscitelli S and Wilkes L Danziger L (1992) Clinical pharmacokinetics

of metronidazole and other nitroimidazole anti-infectives ClinPharmacokinet 23(5)

328-64

44 Hu O Tang A and chang C (1995) Galactosa single point method as a measure of

residual liver function Example of refoperazone kinetics in patient with liver cirrhosis

JClinical pharm 35(3) 250-258

45 Kaneko J(1980) Clinical biochemistry of domestic animals 4th Ed Academic Press

Inc NewYork London 365-391


81


1 INTRODUCTION

Gastrointestinal tract of poultry acts as a reservoir for maintenance of pathogens capable of

inducing diseases[1]

Clostridium perfringensis found in gastrointestinal tract of birds where it

is considered a part of normal bacterial flora[2]

Its etiological agent of a wide range of

diseases in humans and animals[3]

It is an anaerobic rodshape spore forming G +ve bacilli[4]

causing necrotic enteritis in poultry[5]

Necrotic enteritis is infectious diseases in broiler

farms[6]

Its one of most economically important enteric diseases in broilers with mortality

rates up to 50[7]

Its characterized by sudden onset of diarrhea and mucosal necrosis[8]

For many years prophylactic use of antibiotic in feed has been primary means of controlling

necrotic enteritis in broiler industry However development of Clostridium perfringens strain

resistance antibiotic has threatened economic stability of broiler industry[9]

Antimicrobial

therapy is an important tool in reducing enormous losses in poultry industry caused by

bacterial infection[10]

Necrotic enteritis can be prevented by use antibiotics[11]

Among these

antimicrobials amoxicillin and metronidazoleAmoxicillin is a one of most effective β lactam

antibiotic[12]

Its widely used in veterinary medicine because of its broad spectrum

antimicrobial activity good absorption and penetration into tissues[13]

Its bactericidal against

bacteria by inhibition of biosynthesis cell wall mucopeptide during bacterial

multiplication[14]

Metronidazole is antimicrobial agent that has effect on most Gr +ve Gr-ve and anaerobic

bacteria It has antiprotozoal properties[15]

Its active against Clostridium perfringens[16]

The

present study was carried out to evaluate efficacy of amoxicillin and metronidazole either

alone or in combination (Flagymoxreg) against experimentally induced necrotic enteritis in

broiler chickens The in vitro MICs of amoxicillin and metronidazole against Clostridium

perfringens were also determined

2 MATERIALS AND METHODS

21 Drugs

211Amoxicillin

Amoxicillin is semisynthetic broad spectrum penicillin derived from the

basicpenicillinnucleus 6-aminopenicillanic acidIt was used in a therapeutic dose of 20 mgkg

bwt once daily for 5 consecutive days orally or intramuscularly[17]

Amoxicillin

trihydratewas obtained as a pure powder from Sigma Aldrich Chemical Co St Louis USA


82


212 Metronidazole



orally[18]


USA

213 Falgymoxreg





















[19]





83








(a






25 Blood samples


th and 20







analysis




252 Mortality rate




weighed at 1st 10

th and 20







84


















3 RESULTS















85
















th and 20

th day post



20th

day

post

administration

10th

day

post

administration

1st day

post

administration

20th

day

post

administration

10th

day

post

administration

1st day

post

administration

Initial b

wt(20th

day of age)












treated


86






th amp 20

th


20th

day

post administration

10th

day

post administration

1st day



197 160676 196 130944 129 54064 Group 1

195 164405 186 131769 124 56006 Group 2

195 164964 187 133011 125 56515 Group 3

192 163798 186 132739 121 56209 Group 4

198 160884 199 129019 147 52004 Group 5

195 161443 190 132009 139 56014 Group 6

194 161585 190 131461 137 56586 Group 7

194 161605 189 130896 134 57055 Group 8





th and 20

th day




Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

5305plusmn

153

5340plusmn

149

5403plusmn

117

4893plusmn

138

4827plusmn

139

4758plusmn

126

3049plusmn

093

3104plusmn

078

3026plusmn

064 Group 1

5426plusmn

196

5504plusmn

198

5795plusmn

104

4984plusmn

167

5008plusmn

159

5273plusmn

180

3156plusmn

085

3263plusmn

094

3321plusmn

068 Group 2

5317plusmn

162

5389plusmn

142

5794plusmn

113

5037plusmn

159

5028plusmn

147

5205plusmn

143

3098plusmn

073

3206plusmn

089

3354plusmn

089 Group 3

5373plusmn

185

5398plusmn

126

5787plusmn

104

4904plusmn

134

4969plusmn

115

5196plusmn

104

3105plusmn

099

3113plusmn

037

3350plusmn

085 Group 4

5784plusmn

147

5895plusmn

173

5934plusmn

118

5494plusmn

102

5399plusmn

106

5406plusmn

143

3507plusmn

092

3485plusmn

073

3504plusmn

075 Group 5

5347plusmn

199

5408plusmn

186

5788plusmn

117

4918plusmn

178

5020plusmn

155

5296plusmn

144

3108plusmn

069

3226plusmn

099

3284plusmn

069 Group 6

5311plusmn

175

5412plusmn

176

5799plusmn

113

4905plusmn

194

5047plusmn

194

5247plusmn

137

3073plusmn

053

3159plusmn

083

3365plusmn

057 Group 7

5341plusmn

158

5425plusmn

159

5776plusmn

110

4978plusmn

180

5014plusmn

175

5248plusmn

104

3070plusmn

049

3127plusmn

050

3248plusmn

063 Group 8




87






th and 20

th



Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day 1

st day

20th

day

10th

day

1st

day

135plusmn

018

143plusmn

019

123plusmn

015

248plusmn

011 242plusmn

014 264plusmn

016 337plusmn

046 345plusmn

032 326plusmn

018 584plusmn

011

587plusmn

018

590plusmn

012 Group 1

127plusmn

012

144plusmn

014

127plusmn

020

270plusmn

030 253plusmn

032 286plusmn

017 344plusmn

028 363plusmn

049 362plusmn

031 614plusmn

019

616plusmn

024 648plusmn

029 Group 2

127plusmn

016

140plusmn

021

134plusmn

013

264plusmn

025 254plusmn

019 276plusmn

014 339plusmn

036 356plusmn

043 369plusmn

029 600plusmn

028

610plusmn

018

645plusmn

014 Group 3

137plusmn

011

142plusmn

013

138plusmn

020

259plusmn

019 259plusmn

017 261plusmn

018 354plusmn

090 367plusmn

032 359plusmn

023 610plusmn

014

621plusmn

019

620plusmn

018 Group 4

074plusmn 013

075plusmn 014

066plusmn 011

315plusmn 010

310plusmn 006

329plusmn 008

234plusmn 011

232plusmn 031

218plusmn 017

549plusmn 006

542plusmn 007

547plusmn 010

Group 5

128plusmn

016

126plusmn

015

078plusmn

013

255plusmn

016 251plusmn

019 313plusmn

010 327plusmn

039 316plusmn

063 243plusmn

025 549plusmn

015 562plusmn

021 556plusmn

006 Group 6

121plusmn 019

118plusmn 018

078plusmn 012

263plusmn 017

258plusmn 012

318plusmn 014

318plusmn 030

304plusmn 054

247plusmn 022

581plusmn 014

560plusmn 019

565plusmn 008

Group 7

126plusmn

025 119plusmn

021

082plusmn

010

258plusmn

016 261plusmn

019 311plusmn

013 325plusmn

028 313plusmn

039 262plusmn

023 583plusmn

018 574plusmn

026 572plusmn

010 Group 8




88






th and 20

th



Groups

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

145plusmn

016

148plusmn

018

142plusmn

020

498plusmn

023

508plusmn

039

495plusmn

034 Group 1

155plusmn

019

160plusmn

039

209plusmn

012

502plusmn

021

586plusmn

037

663plusmn

046 Group 2

161plusmn

025

162plusmn

017

198plusmn

010

513plusmn

029

562plusmn

049

650plusmn

039 Group 3

147plusmn

020

159plusmn

021

211plusmn

026

499plusmn

035

518plusmn

023

649plusmn

051 Group 4

226plusmn

018

237plusmn

019

241plusmn

020

689plusmn

047

696plusmn

031

685plusmn

026 Group 5

150plusmn

015

161plusmn

019

197plusmn

012

503plusmn

032

523plusmn

020

608plusmn

025 Group 6

148plusmn

017

154plusmn

010

191plusmn

010

510plusmn

021

532plusmn

017

592plusmn

010 Group 7

153plusmn

020

153plusmn

023

199plusmn

009

511plusmn

019

512plusmn

023

578plusmn

011 Group 8








Groups

Thin wall

Mild necrosis

and ulceration

Moderate

necrosis

Severe

necrosis

Healthy 20 0 0 0



(20 mgkg bwt) 40 40 0 0


(40 mgkg bwt) 40 20 0 0




40 0 0 0


89


4 DISCUSSION






Oral













accordance with[29]



found that















who




90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







82


212 Metronidazole



orally[18]


USA

213 Falgymoxreg





















[19]





83








(a






25 Blood samples


th and 20







analysis




252 Mortality rate




weighed at 1st 10

th and 20







84


















3 RESULTS















85
















th and 20

th day post



20th

day

post

administration

10th

day

post

administration

1st day

post

administration

20th

day

post

administration

10th

day

post

administration

1st day

post

administration

Initial b

wt(20th

day of age)












treated


86






th amp 20

th


20th

day

post administration

10th

day

post administration

1st day



197 160676 196 130944 129 54064 Group 1

195 164405 186 131769 124 56006 Group 2

195 164964 187 133011 125 56515 Group 3

192 163798 186 132739 121 56209 Group 4

198 160884 199 129019 147 52004 Group 5

195 161443 190 132009 139 56014 Group 6

194 161585 190 131461 137 56586 Group 7

194 161605 189 130896 134 57055 Group 8





th and 20

th day




Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

5305plusmn

153

5340plusmn

149

5403plusmn

117

4893plusmn

138

4827plusmn

139

4758plusmn

126

3049plusmn

093

3104plusmn

078

3026plusmn

064 Group 1

5426plusmn

196

5504plusmn

198

5795plusmn

104

4984plusmn

167

5008plusmn

159

5273plusmn

180

3156plusmn

085

3263plusmn

094

3321plusmn

068 Group 2

5317plusmn

162

5389plusmn

142

5794plusmn

113

5037plusmn

159

5028plusmn

147

5205plusmn

143

3098plusmn

073

3206plusmn

089

3354plusmn

089 Group 3

5373plusmn

185

5398plusmn

126

5787plusmn

104

4904plusmn

134

4969plusmn

115

5196plusmn

104

3105plusmn

099

3113plusmn

037

3350plusmn

085 Group 4

5784plusmn

147

5895plusmn

173

5934plusmn

118

5494plusmn

102

5399plusmn

106

5406plusmn

143

3507plusmn

092

3485plusmn

073

3504plusmn

075 Group 5

5347plusmn

199

5408plusmn

186

5788plusmn

117

4918plusmn

178

5020plusmn

155

5296plusmn

144

3108plusmn

069

3226plusmn

099

3284plusmn

069 Group 6

5311plusmn

175

5412plusmn

176

5799plusmn

113

4905plusmn

194

5047plusmn

194

5247plusmn

137

3073plusmn

053

3159plusmn

083

3365plusmn

057 Group 7

5341plusmn

158

5425plusmn

159

5776plusmn

110

4978plusmn

180

5014plusmn

175

5248plusmn

104

3070plusmn

049

3127plusmn

050

3248plusmn

063 Group 8




87






th and 20

th



Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day 1

st day

20th

day

10th

day

1st

day

135plusmn

018

143plusmn

019

123plusmn

015

248plusmn

011 242plusmn

014 264plusmn

016 337plusmn

046 345plusmn

032 326plusmn

018 584plusmn

011

587plusmn

018

590plusmn

012 Group 1

127plusmn

012

144plusmn

014

127plusmn

020

270plusmn

030 253plusmn

032 286plusmn

017 344plusmn

028 363plusmn

049 362plusmn

031 614plusmn

019

616plusmn

024 648plusmn

029 Group 2

127plusmn

016

140plusmn

021

134plusmn

013

264plusmn

025 254plusmn

019 276plusmn

014 339plusmn

036 356plusmn

043 369plusmn

029 600plusmn

028

610plusmn

018

645plusmn

014 Group 3

137plusmn

011

142plusmn

013

138plusmn

020

259plusmn

019 259plusmn

017 261plusmn

018 354plusmn

090 367plusmn

032 359plusmn

023 610plusmn

014

621plusmn

019

620plusmn

018 Group 4

074plusmn 013

075plusmn 014

066plusmn 011

315plusmn 010

310plusmn 006

329plusmn 008

234plusmn 011

232plusmn 031

218plusmn 017

549plusmn 006

542plusmn 007

547plusmn 010

Group 5

128plusmn

016

126plusmn

015

078plusmn

013

255plusmn

016 251plusmn

019 313plusmn

010 327plusmn

039 316plusmn

063 243plusmn

025 549plusmn

015 562plusmn

021 556plusmn

006 Group 6

121plusmn 019

118plusmn 018

078plusmn 012

263plusmn 017

258plusmn 012

318plusmn 014

318plusmn 030

304plusmn 054

247plusmn 022

581plusmn 014

560plusmn 019

565plusmn 008

Group 7

126plusmn

025 119plusmn

021

082plusmn

010

258plusmn

016 261plusmn

019 311plusmn

013 325plusmn

028 313plusmn

039 262plusmn

023 583plusmn

018 574plusmn

026 572plusmn

010 Group 8




88






th and 20

th



Groups

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

145plusmn

016

148plusmn

018

142plusmn

020

498plusmn

023

508plusmn

039

495plusmn

034 Group 1

155plusmn

019

160plusmn

039

209plusmn

012

502plusmn

021

586plusmn

037

663plusmn

046 Group 2

161plusmn

025

162plusmn

017

198plusmn

010

513plusmn

029

562plusmn

049

650plusmn

039 Group 3

147plusmn

020

159plusmn

021

211plusmn

026

499plusmn

035

518plusmn

023

649plusmn

051 Group 4

226plusmn

018

237plusmn

019

241plusmn

020

689plusmn

047

696plusmn

031

685plusmn

026 Group 5

150plusmn

015

161plusmn

019

197plusmn

012

503plusmn

032

523plusmn

020

608plusmn

025 Group 6

148plusmn

017

154plusmn

010

191plusmn

010

510plusmn

021

532plusmn

017

592plusmn

010 Group 7

153plusmn

020

153plusmn

023

199plusmn

009

511plusmn

019

512plusmn

023

578plusmn

011 Group 8








Groups

Thin wall

Mild necrosis

and ulceration

Moderate

necrosis

Severe

necrosis

Healthy 20 0 0 0



(20 mgkg bwt) 40 40 0 0


(40 mgkg bwt) 40 20 0 0




40 0 0 0


89


4 DISCUSSION






Oral













accordance with[29]



found that















who




90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







83








(a






25 Blood samples


th and 20







analysis




252 Mortality rate




weighed at 1st 10

th and 20







84


















3 RESULTS















85
















th and 20

th day post



20th

day

post

administration

10th

day

post

administration

1st day

post

administration

20th

day

post

administration

10th

day

post

administration

1st day

post

administration

Initial b

wt(20th

day of age)












treated


86






th amp 20

th


20th

day

post administration

10th

day

post administration

1st day



197 160676 196 130944 129 54064 Group 1

195 164405 186 131769 124 56006 Group 2

195 164964 187 133011 125 56515 Group 3

192 163798 186 132739 121 56209 Group 4

198 160884 199 129019 147 52004 Group 5

195 161443 190 132009 139 56014 Group 6

194 161585 190 131461 137 56586 Group 7

194 161605 189 130896 134 57055 Group 8





th and 20

th day




Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

5305plusmn

153

5340plusmn

149

5403plusmn

117

4893plusmn

138

4827plusmn

139

4758plusmn

126

3049plusmn

093

3104plusmn

078

3026plusmn

064 Group 1

5426plusmn

196

5504plusmn

198

5795plusmn

104

4984plusmn

167

5008plusmn

159

5273plusmn

180

3156plusmn

085

3263plusmn

094

3321plusmn

068 Group 2

5317plusmn

162

5389plusmn

142

5794plusmn

113

5037plusmn

159

5028plusmn

147

5205plusmn

143

3098plusmn

073

3206plusmn

089

3354plusmn

089 Group 3

5373plusmn

185

5398plusmn

126

5787plusmn

104

4904plusmn

134

4969plusmn

115

5196plusmn

104

3105plusmn

099

3113plusmn

037

3350plusmn

085 Group 4

5784plusmn

147

5895plusmn

173

5934plusmn

118

5494plusmn

102

5399plusmn

106

5406plusmn

143

3507plusmn

092

3485plusmn

073

3504plusmn

075 Group 5

5347plusmn

199

5408plusmn

186

5788plusmn

117

4918plusmn

178

5020plusmn

155

5296plusmn

144

3108plusmn

069

3226plusmn

099

3284plusmn

069 Group 6

5311plusmn

175

5412plusmn

176

5799plusmn

113

4905plusmn

194

5047plusmn

194

5247plusmn

137

3073plusmn

053

3159plusmn

083

3365plusmn

057 Group 7

5341plusmn

158

5425plusmn

159

5776plusmn

110

4978plusmn

180

5014plusmn

175

5248plusmn

104

3070plusmn

049

3127plusmn

050

3248plusmn

063 Group 8




87






th and 20

th



Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day 1

st day

20th

day

10th

day

1st

day

135plusmn

018

143plusmn

019

123plusmn

015

248plusmn

011 242plusmn

014 264plusmn

016 337plusmn

046 345plusmn

032 326plusmn

018 584plusmn

011

587plusmn

018

590plusmn

012 Group 1

127plusmn

012

144plusmn

014

127plusmn

020

270plusmn

030 253plusmn

032 286plusmn

017 344plusmn

028 363plusmn

049 362plusmn

031 614plusmn

019

616plusmn

024 648plusmn

029 Group 2

127plusmn

016

140plusmn

021

134plusmn

013

264plusmn

025 254plusmn

019 276plusmn

014 339plusmn

036 356plusmn

043 369plusmn

029 600plusmn

028

610plusmn

018

645plusmn

014 Group 3

137plusmn

011

142plusmn

013

138plusmn

020

259plusmn

019 259plusmn

017 261plusmn

018 354plusmn

090 367plusmn

032 359plusmn

023 610plusmn

014

621plusmn

019

620plusmn

018 Group 4

074plusmn 013

075plusmn 014

066plusmn 011

315plusmn 010

310plusmn 006

329plusmn 008

234plusmn 011

232plusmn 031

218plusmn 017

549plusmn 006

542plusmn 007

547plusmn 010

Group 5

128plusmn

016

126plusmn

015

078plusmn

013

255plusmn

016 251plusmn

019 313plusmn

010 327plusmn

039 316plusmn

063 243plusmn

025 549plusmn

015 562plusmn

021 556plusmn

006 Group 6

121plusmn 019

118plusmn 018

078plusmn 012

263plusmn 017

258plusmn 012

318plusmn 014

318plusmn 030

304plusmn 054

247plusmn 022

581plusmn 014

560plusmn 019

565plusmn 008

Group 7

126plusmn

025 119plusmn

021

082plusmn

010

258plusmn

016 261plusmn

019 311plusmn

013 325plusmn

028 313plusmn

039 262plusmn

023 583plusmn

018 574plusmn

026 572plusmn

010 Group 8




88






th and 20

th



Groups

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

145plusmn

016

148plusmn

018

142plusmn

020

498plusmn

023

508plusmn

039

495plusmn

034 Group 1

155plusmn

019

160plusmn

039

209plusmn

012

502plusmn

021

586plusmn

037

663plusmn

046 Group 2

161plusmn

025

162plusmn

017

198plusmn

010

513plusmn

029

562plusmn

049

650plusmn

039 Group 3

147plusmn

020

159plusmn

021

211plusmn

026

499plusmn

035

518plusmn

023

649plusmn

051 Group 4

226plusmn

018

237plusmn

019

241plusmn

020

689plusmn

047

696plusmn

031

685plusmn

026 Group 5

150plusmn

015

161plusmn

019

197plusmn

012

503plusmn

032

523plusmn

020

608plusmn

025 Group 6

148plusmn

017

154plusmn

010

191plusmn

010

510plusmn

021

532plusmn

017

592plusmn

010 Group 7

153plusmn

020

153plusmn

023

199plusmn

009

511plusmn

019

512plusmn

023

578plusmn

011 Group 8








Groups

Thin wall

Mild necrosis

and ulceration

Moderate

necrosis

Severe

necrosis

Healthy 20 0 0 0



(20 mgkg bwt) 40 40 0 0


(40 mgkg bwt) 40 20 0 0




40 0 0 0


89


4 DISCUSSION






Oral













accordance with[29]



found that















who




90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







84


















3 RESULTS















85
















th and 20

th day post



20th

day

post

administration

10th

day

post

administration

1st day

post

administration

20th

day

post

administration

10th

day

post

administration

1st day

post

administration

Initial b

wt(20th

day of age)












treated


86






th amp 20

th


20th

day

post administration

10th

day

post administration

1st day



197 160676 196 130944 129 54064 Group 1

195 164405 186 131769 124 56006 Group 2

195 164964 187 133011 125 56515 Group 3

192 163798 186 132739 121 56209 Group 4

198 160884 199 129019 147 52004 Group 5

195 161443 190 132009 139 56014 Group 6

194 161585 190 131461 137 56586 Group 7

194 161605 189 130896 134 57055 Group 8





th and 20

th day




Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

5305plusmn

153

5340plusmn

149

5403plusmn

117

4893plusmn

138

4827plusmn

139

4758plusmn

126

3049plusmn

093

3104plusmn

078

3026plusmn

064 Group 1

5426plusmn

196

5504plusmn

198

5795plusmn

104

4984plusmn

167

5008plusmn

159

5273plusmn

180

3156plusmn

085

3263plusmn

094

3321plusmn

068 Group 2

5317plusmn

162

5389plusmn

142

5794plusmn

113

5037plusmn

159

5028plusmn

147

5205plusmn

143

3098plusmn

073

3206plusmn

089

3354plusmn

089 Group 3

5373plusmn

185

5398plusmn

126

5787plusmn

104

4904plusmn

134

4969plusmn

115

5196plusmn

104

3105plusmn

099

3113plusmn

037

3350plusmn

085 Group 4

5784plusmn

147

5895plusmn

173

5934plusmn

118

5494plusmn

102

5399plusmn

106

5406plusmn

143

3507plusmn

092

3485plusmn

073

3504plusmn

075 Group 5

5347plusmn

199

5408plusmn

186

5788plusmn

117

4918plusmn

178

5020plusmn

155

5296plusmn

144

3108plusmn

069

3226plusmn

099

3284plusmn

069 Group 6

5311plusmn

175

5412plusmn

176

5799plusmn

113

4905plusmn

194

5047plusmn

194

5247plusmn

137

3073plusmn

053

3159plusmn

083

3365plusmn

057 Group 7

5341plusmn

158

5425plusmn

159

5776plusmn

110

4978plusmn

180

5014plusmn

175

5248plusmn

104

3070plusmn

049

3127plusmn

050

3248plusmn

063 Group 8




87






th and 20

th



Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day 1

st day

20th

day

10th

day

1st

day

135plusmn

018

143plusmn

019

123plusmn

015

248plusmn

011 242plusmn

014 264plusmn

016 337plusmn

046 345plusmn

032 326plusmn

018 584plusmn

011

587plusmn

018

590plusmn

012 Group 1

127plusmn

012

144plusmn

014

127plusmn

020

270plusmn

030 253plusmn

032 286plusmn

017 344plusmn

028 363plusmn

049 362plusmn

031 614plusmn

019

616plusmn

024 648plusmn

029 Group 2

127plusmn

016

140plusmn

021

134plusmn

013

264plusmn

025 254plusmn

019 276plusmn

014 339plusmn

036 356plusmn

043 369plusmn

029 600plusmn

028

610plusmn

018

645plusmn

014 Group 3

137plusmn

011

142plusmn

013

138plusmn

020

259plusmn

019 259plusmn

017 261plusmn

018 354plusmn

090 367plusmn

032 359plusmn

023 610plusmn

014

621plusmn

019

620plusmn

018 Group 4

074plusmn 013

075plusmn 014

066plusmn 011

315plusmn 010

310plusmn 006

329plusmn 008

234plusmn 011

232plusmn 031

218plusmn 017

549plusmn 006

542plusmn 007

547plusmn 010

Group 5

128plusmn

016

126plusmn

015

078plusmn

013

255plusmn

016 251plusmn

019 313plusmn

010 327plusmn

039 316plusmn

063 243plusmn

025 549plusmn

015 562plusmn

021 556plusmn

006 Group 6

121plusmn 019

118plusmn 018

078plusmn 012

263plusmn 017

258plusmn 012

318plusmn 014

318plusmn 030

304plusmn 054

247plusmn 022

581plusmn 014

560plusmn 019

565plusmn 008

Group 7

126plusmn

025 119plusmn

021

082plusmn

010

258plusmn

016 261plusmn

019 311plusmn

013 325plusmn

028 313plusmn

039 262plusmn

023 583plusmn

018 574plusmn

026 572plusmn

010 Group 8




88






th and 20

th



Groups

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

145plusmn

016

148plusmn

018

142plusmn

020

498plusmn

023

508plusmn

039

495plusmn

034 Group 1

155plusmn

019

160plusmn

039

209plusmn

012

502plusmn

021

586plusmn

037

663plusmn

046 Group 2

161plusmn

025

162plusmn

017

198plusmn

010

513plusmn

029

562plusmn

049

650plusmn

039 Group 3

147plusmn

020

159plusmn

021

211plusmn

026

499plusmn

035

518plusmn

023

649plusmn

051 Group 4

226plusmn

018

237plusmn

019

241plusmn

020

689plusmn

047

696plusmn

031

685plusmn

026 Group 5

150plusmn

015

161plusmn

019

197plusmn

012

503plusmn

032

523plusmn

020

608plusmn

025 Group 6

148plusmn

017

154plusmn

010

191plusmn

010

510plusmn

021

532plusmn

017

592plusmn

010 Group 7

153plusmn

020

153plusmn

023

199plusmn

009

511plusmn

019

512plusmn

023

578plusmn

011 Group 8








Groups

Thin wall

Mild necrosis

and ulceration

Moderate

necrosis

Severe

necrosis

Healthy 20 0 0 0



(20 mgkg bwt) 40 40 0 0


(40 mgkg bwt) 40 20 0 0




40 0 0 0


89


4 DISCUSSION






Oral













accordance with[29]



found that















who




90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







85
















th and 20

th day post



20th

day

post

administration

10th

day

post

administration

1st day

post

administration

20th

day

post

administration

10th

day

post

administration

1st day

post

administration

Initial b

wt(20th

day of age)












treated


86






th amp 20

th


20th

day

post administration

10th

day

post administration

1st day



197 160676 196 130944 129 54064 Group 1

195 164405 186 131769 124 56006 Group 2

195 164964 187 133011 125 56515 Group 3

192 163798 186 132739 121 56209 Group 4

198 160884 199 129019 147 52004 Group 5

195 161443 190 132009 139 56014 Group 6

194 161585 190 131461 137 56586 Group 7

194 161605 189 130896 134 57055 Group 8





th and 20

th day




Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

5305plusmn

153

5340plusmn

149

5403plusmn

117

4893plusmn

138

4827plusmn

139

4758plusmn

126

3049plusmn

093

3104plusmn

078

3026plusmn

064 Group 1

5426plusmn

196

5504plusmn

198

5795plusmn

104

4984plusmn

167

5008plusmn

159

5273plusmn

180

3156plusmn

085

3263plusmn

094

3321plusmn

068 Group 2

5317plusmn

162

5389plusmn

142

5794plusmn

113

5037plusmn

159

5028plusmn

147

5205plusmn

143

3098plusmn

073

3206plusmn

089

3354plusmn

089 Group 3

5373plusmn

185

5398plusmn

126

5787plusmn

104

4904plusmn

134

4969plusmn

115

5196plusmn

104

3105plusmn

099

3113plusmn

037

3350plusmn

085 Group 4

5784plusmn

147

5895plusmn

173

5934plusmn

118

5494plusmn

102

5399plusmn

106

5406plusmn

143

3507plusmn

092

3485plusmn

073

3504plusmn

075 Group 5

5347plusmn

199

5408plusmn

186

5788plusmn

117

4918plusmn

178

5020plusmn

155

5296plusmn

144

3108plusmn

069

3226plusmn

099

3284plusmn

069 Group 6

5311plusmn

175

5412plusmn

176

5799plusmn

113

4905plusmn

194

5047plusmn

194

5247plusmn

137

3073plusmn

053

3159plusmn

083

3365plusmn

057 Group 7

5341plusmn

158

5425plusmn

159

5776plusmn

110

4978plusmn

180

5014plusmn

175

5248plusmn

104

3070plusmn

049

3127plusmn

050

3248plusmn

063 Group 8




87






th and 20

th



Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day 1

st day

20th

day

10th

day

1st

day

135plusmn

018

143plusmn

019

123plusmn

015

248plusmn

011 242plusmn

014 264plusmn

016 337plusmn

046 345plusmn

032 326plusmn

018 584plusmn

011

587plusmn

018

590plusmn

012 Group 1

127plusmn

012

144plusmn

014

127plusmn

020

270plusmn

030 253plusmn

032 286plusmn

017 344plusmn

028 363plusmn

049 362plusmn

031 614plusmn

019

616plusmn

024 648plusmn

029 Group 2

127plusmn

016

140plusmn

021

134plusmn

013

264plusmn

025 254plusmn

019 276plusmn

014 339plusmn

036 356plusmn

043 369plusmn

029 600plusmn

028

610plusmn

018

645plusmn

014 Group 3

137plusmn

011

142plusmn

013

138plusmn

020

259plusmn

019 259plusmn

017 261plusmn

018 354plusmn

090 367plusmn

032 359plusmn

023 610plusmn

014

621plusmn

019

620plusmn

018 Group 4

074plusmn 013

075plusmn 014

066plusmn 011

315plusmn 010

310plusmn 006

329plusmn 008

234plusmn 011

232plusmn 031

218plusmn 017

549plusmn 006

542plusmn 007

547plusmn 010

Group 5

128plusmn

016

126plusmn

015

078plusmn

013

255plusmn

016 251plusmn

019 313plusmn

010 327plusmn

039 316plusmn

063 243plusmn

025 549plusmn

015 562plusmn

021 556plusmn

006 Group 6

121plusmn 019

118plusmn 018

078plusmn 012

263plusmn 017

258plusmn 012

318plusmn 014

318plusmn 030

304plusmn 054

247plusmn 022

581plusmn 014

560plusmn 019

565plusmn 008

Group 7

126plusmn

025 119plusmn

021

082plusmn

010

258plusmn

016 261plusmn

019 311plusmn

013 325plusmn

028 313plusmn

039 262plusmn

023 583plusmn

018 574plusmn

026 572plusmn

010 Group 8




88






th and 20

th



Groups

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

145plusmn

016

148plusmn

018

142plusmn

020

498plusmn

023

508plusmn

039

495plusmn

034 Group 1

155plusmn

019

160plusmn

039

209plusmn

012

502plusmn

021

586plusmn

037

663plusmn

046 Group 2

161plusmn

025

162plusmn

017

198plusmn

010

513plusmn

029

562plusmn

049

650plusmn

039 Group 3

147plusmn

020

159plusmn

021

211plusmn

026

499plusmn

035

518plusmn

023

649plusmn

051 Group 4

226plusmn

018

237plusmn

019

241plusmn

020

689plusmn

047

696plusmn

031

685plusmn

026 Group 5

150plusmn

015

161plusmn

019

197plusmn

012

503plusmn

032

523plusmn

020

608plusmn

025 Group 6

148plusmn

017

154plusmn

010

191plusmn

010

510plusmn

021

532plusmn

017

592plusmn

010 Group 7

153plusmn

020

153plusmn

023

199plusmn

009

511plusmn

019

512plusmn

023

578plusmn

011 Group 8








Groups

Thin wall

Mild necrosis

and ulceration

Moderate

necrosis

Severe

necrosis

Healthy 20 0 0 0



(20 mgkg bwt) 40 40 0 0


(40 mgkg bwt) 40 20 0 0




40 0 0 0


89


4 DISCUSSION






Oral













accordance with[29]



found that















who




90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







86






th amp 20

th


20th

day

post administration

10th

day

post administration

1st day



197 160676 196 130944 129 54064 Group 1

195 164405 186 131769 124 56006 Group 2

195 164964 187 133011 125 56515 Group 3

192 163798 186 132739 121 56209 Group 4

198 160884 199 129019 147 52004 Group 5

195 161443 190 132009 139 56014 Group 6

194 161585 190 131461 137 56586 Group 7

194 161605 189 130896 134 57055 Group 8





th and 20

th day




Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

5305plusmn

153

5340plusmn

149

5403plusmn

117

4893plusmn

138

4827plusmn

139

4758plusmn

126

3049plusmn

093

3104plusmn

078

3026plusmn

064 Group 1

5426plusmn

196

5504plusmn

198

5795plusmn

104

4984plusmn

167

5008plusmn

159

5273plusmn

180

3156plusmn

085

3263plusmn

094

3321plusmn

068 Group 2

5317plusmn

162

5389plusmn

142

5794plusmn

113

5037plusmn

159

5028plusmn

147

5205plusmn

143

3098plusmn

073

3206plusmn

089

3354plusmn

089 Group 3

5373plusmn

185

5398plusmn

126

5787plusmn

104

4904plusmn

134

4969plusmn

115

5196plusmn

104

3105plusmn

099

3113plusmn

037

3350plusmn

085 Group 4

5784plusmn

147

5895plusmn

173

5934plusmn

118

5494plusmn

102

5399plusmn

106

5406plusmn

143

3507plusmn

092

3485plusmn

073

3504plusmn

075 Group 5

5347plusmn

199

5408plusmn

186

5788plusmn

117

4918plusmn

178

5020plusmn

155

5296plusmn

144

3108plusmn

069

3226plusmn

099

3284plusmn

069 Group 6

5311plusmn

175

5412plusmn

176

5799plusmn

113

4905plusmn

194

5047plusmn

194

5247plusmn

137

3073plusmn

053

3159plusmn

083

3365plusmn

057 Group 7

5341plusmn

158

5425plusmn

159

5776plusmn

110

4978plusmn

180

5014plusmn

175

5248plusmn

104

3070plusmn

049

3127plusmn

050

3248plusmn

063 Group 8




87






th and 20

th



Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day 1

st day

20th

day

10th

day

1st

day

135plusmn

018

143plusmn

019

123plusmn

015

248plusmn

011 242plusmn

014 264plusmn

016 337plusmn

046 345plusmn

032 326plusmn

018 584plusmn

011

587plusmn

018

590plusmn

012 Group 1

127plusmn

012

144plusmn

014

127plusmn

020

270plusmn

030 253plusmn

032 286plusmn

017 344plusmn

028 363plusmn

049 362plusmn

031 614plusmn

019

616plusmn

024 648plusmn

029 Group 2

127plusmn

016

140plusmn

021

134plusmn

013

264plusmn

025 254plusmn

019 276plusmn

014 339plusmn

036 356plusmn

043 369plusmn

029 600plusmn

028

610plusmn

018

645plusmn

014 Group 3

137plusmn

011

142plusmn

013

138plusmn

020

259plusmn

019 259plusmn

017 261plusmn

018 354plusmn

090 367plusmn

032 359plusmn

023 610plusmn

014

621plusmn

019

620plusmn

018 Group 4

074plusmn 013

075plusmn 014

066plusmn 011

315plusmn 010

310plusmn 006

329plusmn 008

234plusmn 011

232plusmn 031

218plusmn 017

549plusmn 006

542plusmn 007

547plusmn 010

Group 5

128plusmn

016

126plusmn

015

078plusmn

013

255plusmn

016 251plusmn

019 313plusmn

010 327plusmn

039 316plusmn

063 243plusmn

025 549plusmn

015 562plusmn

021 556plusmn

006 Group 6

121plusmn 019

118plusmn 018

078plusmn 012

263plusmn 017

258plusmn 012

318plusmn 014

318plusmn 030

304plusmn 054

247plusmn 022

581plusmn 014

560plusmn 019

565plusmn 008

Group 7

126plusmn

025 119plusmn

021

082plusmn

010

258plusmn

016 261plusmn

019 311plusmn

013 325plusmn

028 313plusmn

039 262plusmn

023 583plusmn

018 574plusmn

026 572plusmn

010 Group 8




88






th and 20

th



Groups

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

145plusmn

016

148plusmn

018

142plusmn

020

498plusmn

023

508plusmn

039

495plusmn

034 Group 1

155plusmn

019

160plusmn

039

209plusmn

012

502plusmn

021

586plusmn

037

663plusmn

046 Group 2

161plusmn

025

162plusmn

017

198plusmn

010

513plusmn

029

562plusmn

049

650plusmn

039 Group 3

147plusmn

020

159plusmn

021

211plusmn

026

499plusmn

035

518plusmn

023

649plusmn

051 Group 4

226plusmn

018

237plusmn

019

241plusmn

020

689plusmn

047

696plusmn

031

685plusmn

026 Group 5

150plusmn

015

161plusmn

019

197plusmn

012

503plusmn

032

523plusmn

020

608plusmn

025 Group 6

148plusmn

017

154plusmn

010

191plusmn

010

510plusmn

021

532plusmn

017

592plusmn

010 Group 7

153plusmn

020

153plusmn

023

199plusmn

009

511plusmn

019

512plusmn

023

578plusmn

011 Group 8








Groups

Thin wall

Mild necrosis

and ulceration

Moderate

necrosis

Severe

necrosis

Healthy 20 0 0 0



(20 mgkg bwt) 40 40 0 0


(40 mgkg bwt) 40 20 0 0




40 0 0 0


89


4 DISCUSSION






Oral













accordance with[29]



found that















who




90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







87






th and 20

th



Groups 20

th

day

10th

day

1st

day

20th

day

10th

day

1st

day

20th

day

10th

day 1

st day

20th

day

10th

day

1st

day

135plusmn

018

143plusmn

019

123plusmn

015

248plusmn

011 242plusmn

014 264plusmn

016 337plusmn

046 345plusmn

032 326plusmn

018 584plusmn

011

587plusmn

018

590plusmn

012 Group 1

127plusmn

012

144plusmn

014

127plusmn

020

270plusmn

030 253plusmn

032 286plusmn

017 344plusmn

028 363plusmn

049 362plusmn

031 614plusmn

019

616plusmn

024 648plusmn

029 Group 2

127plusmn

016

140plusmn

021

134plusmn

013

264plusmn

025 254plusmn

019 276plusmn

014 339plusmn

036 356plusmn

043 369plusmn

029 600plusmn

028

610plusmn

018

645plusmn

014 Group 3

137plusmn

011

142plusmn

013

138plusmn

020

259plusmn

019 259plusmn

017 261plusmn

018 354plusmn

090 367plusmn

032 359plusmn

023 610plusmn

014

621plusmn

019

620plusmn

018 Group 4

074plusmn 013

075plusmn 014

066plusmn 011

315plusmn 010

310plusmn 006

329plusmn 008

234plusmn 011

232plusmn 031

218plusmn 017

549plusmn 006

542plusmn 007

547plusmn 010

Group 5

128plusmn

016

126plusmn

015

078plusmn

013

255plusmn

016 251plusmn

019 313plusmn

010 327plusmn

039 316plusmn

063 243plusmn

025 549plusmn

015 562plusmn

021 556plusmn

006 Group 6

121plusmn 019

118plusmn 018

078plusmn 012

263plusmn 017

258plusmn 012

318plusmn 014

318plusmn 030

304plusmn 054

247plusmn 022

581plusmn 014

560plusmn 019

565plusmn 008

Group 7

126plusmn

025 119plusmn

021

082plusmn

010

258plusmn

016 261plusmn

019 311plusmn

013 325plusmn

028 313plusmn

039 262plusmn

023 583plusmn

018 574plusmn

026 572plusmn

010 Group 8




88






th and 20

th



Groups

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

145plusmn

016

148plusmn

018

142plusmn

020

498plusmn

023

508plusmn

039

495plusmn

034 Group 1

155plusmn

019

160plusmn

039

209plusmn

012

502plusmn

021

586plusmn

037

663plusmn

046 Group 2

161plusmn

025

162plusmn

017

198plusmn

010

513plusmn

029

562plusmn

049

650plusmn

039 Group 3

147plusmn

020

159plusmn

021

211plusmn

026

499plusmn

035

518plusmn

023

649plusmn

051 Group 4

226plusmn

018

237plusmn

019

241plusmn

020

689plusmn

047

696plusmn

031

685plusmn

026 Group 5

150plusmn

015

161plusmn

019

197plusmn

012

503plusmn

032

523plusmn

020

608plusmn

025 Group 6

148plusmn

017

154plusmn

010

191plusmn

010

510plusmn

021

532plusmn

017

592plusmn

010 Group 7

153plusmn

020

153plusmn

023

199plusmn

009

511plusmn

019

512plusmn

023

578plusmn

011 Group 8








Groups

Thin wall

Mild necrosis

and ulceration

Moderate

necrosis

Severe

necrosis

Healthy 20 0 0 0



(20 mgkg bwt) 40 40 0 0


(40 mgkg bwt) 40 20 0 0




40 0 0 0


89


4 DISCUSSION






Oral













accordance with[29]



found that















who




90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







88






th and 20

th



Groups

20th

day

10th

day

1st

day

20th

day

10th

day

1st

day

145plusmn

016

148plusmn

018

142plusmn

020

498plusmn

023

508plusmn

039

495plusmn

034 Group 1

155plusmn

019

160plusmn

039

209plusmn

012

502plusmn

021

586plusmn

037

663plusmn

046 Group 2

161plusmn

025

162plusmn

017

198plusmn

010

513plusmn

029

562plusmn

049

650plusmn

039 Group 3

147plusmn

020

159plusmn

021

211plusmn

026

499plusmn

035

518plusmn

023

649plusmn

051 Group 4

226plusmn

018

237plusmn

019

241plusmn

020

689plusmn

047

696plusmn

031

685plusmn

026 Group 5

150plusmn

015

161plusmn

019

197plusmn

012

503plusmn

032

523plusmn

020

608plusmn

025 Group 6

148plusmn

017

154plusmn

010

191plusmn

010

510plusmn

021

532plusmn

017

592plusmn

010 Group 7

153plusmn

020

153plusmn

023

199plusmn

009

511plusmn

019

512plusmn

023

578plusmn

011 Group 8








Groups

Thin wall

Mild necrosis

and ulceration

Moderate

necrosis

Severe

necrosis

Healthy 20 0 0 0



(20 mgkg bwt) 40 40 0 0


(40 mgkg bwt) 40 20 0 0




40 0 0 0


89


4 DISCUSSION






Oral













accordance with[29]



found that















who




90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







89


4 DISCUSSION






Oral













accordance with[29]



found that















who




90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







90



They found










enteritis[33]






gain[35]

















infections[39]







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







91



th and 20

th day post






metabolic activity





by[42]




Regarding broiler





albumin[40]




th

and 20th



who reported










Infected



92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







92




th and 20




CONCLUSIONS





ACKNOWLEDGMENT





REFERENCES








225-235












93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







93





792-798



Science 80 1451-1454


Vet Rec 99 84-85








233


179-181








2 340ndash352










94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







94



University






81(1) 61ndash69






Masoura 1393-1205




Company Boston



262-264








63-68







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64







95



432-1955



Toxicol 66(5) 329-334



Liayed- Luke London







University



328-64






efficacy of flagymox (amoxicillin and metronidazole

Documents