Ab. Hamid, Hasiah

Abdullah, Abdul Salam

Hussain, Mohd Khairi

Rajion, Mohamed Ali

Universiti Putra Malaysia Institutional Repository

UPM Research Report 1998: Volume 2THE USE OF ENZYME INDUCERS IN PREVENTINGSIGNAL GRASS (BRACHIARIA DECUMBENS)TOXICITY IN SHEEPA. Salam Abdullah, A.H. Hasiah, H.M. Khairi andM.A. RajionFaculty of Medicine and Health SciencesUniversiti Putra Malaysia, 43400 UPM, Serdang, Selangor,MalaysiaKeywords: Brachiaria decumbens, toxicity, sheep, en-zyme, induction.IntroductionSignal grass (B. decumbens) causes severe hepatic damage insheep. The affected sheep normally died. ~ter se~eral weeksof continuous grazing on this grass. Initial studle~ showedthat B. decumbens toxicity in sheep may be partially pre-vented by adding 1 gmlliter of zinc sulphate in their drinkingwater (Salam Abdullah et al. 1994). The mechanism of pro-tection by zinc from the toxic effect of B. decumbens may bedue to the binding of the toxic compounds. from ~. decu,!,-bens with zinc in the rumen of sheep. In view of Its partialprotection, the study using zinc sulphate to prevent this t~x-icity was discontinued and zinc sulphate was replaced Withenzyme inducers such as phenobarbit~ne, prochloraz andgriseofulvin. The purpose of this study IS to.lOcrease the en-zyme activities in sheep and subsequently increase the de-toxification of the toxic substance. The study on the ~h.em?-protective role of phenobarbitone in B. decumbens tOXICIty10sheep has been completed.Materials and Methods. Twenty six healthy young adult Wiltshire and IndigenousMalaysian crossbred rams (14-16 months of ag~) were usedin this study. They were divided in 4 groups 1,e Group A(control); Group B (Phenobarbitone only) Group C (Pheno-barbitone and B. decumbens) and Group D (B. decumbensonly). All animals in Group B and C were given phenobar-bitone orally at the dose rate of 30mglkg body weight forfive consecutive days one week before allowing than them tograze on B. decumbens. The administration of phenobarbi-tone was continued for three consecutive days every twoweeks till until the end of the study. The animals in Group Aand B were fed cut grass such as Mardi Digit (Digitaria Seti-valva) and Guinea grass (Panicum maximum). All animalswere provided with feed concentrate daily, mineralized sa~tlicks and water ad libitum till the end of ten weeks expen-mental period. All animals with severe signs of B. decum-bens toxicity were sacrificed immediately while those whichdid not show any toxic signs and the control group were sac-rificed at the end of ten weeks. Liver and kidney sampleswere collected and kept frozen in liquid nitrogen until en-zyme assay were performed. The activities of aminopyrine-N-demethylase and aniline-a-hydroxylase and cytochrome P-450 were determined according to the methods described byMazel (1971). The enzymatic activities of UPP glucuronyl-transferase and was determined according to the method ofDutton and Storey (1962).Results and DiscussionTwo animals in group C and seven animals in group D de-veloped signs of B. decumbens poisoning 6-7 weeks and 4-8weeks respectively after continuous grazing on B. decumbenspasture. The signs observed were similar to the signs re-102ported earlier by Salam Abdullah et al. (1989, 1990). Oneanimal in Group D did not develop any toxic signs until theend of the experiment. None of the animals in Group A andB developed any signs of toxicity. The enzyme activity inthe liver and kidney of all the animals are shown in Table 1.The activity of Cytochrome P-450 and Aniline-a-hydroxylase in the liver of B. decumbens treated sheep de-creased significantly (p<O.OOI) compared to the controlgroup. Meanwhile the activity of Aminopyrine-N-demethylase and UDP glucuronyltranferase also decreasedsignificantly (p<0.05). However, there were no significantdifference (p>0.05) in the activity of all enzymes occurredexcept Aminopyrine-N-demethylase which decreased sig-nificantly (p<O.OOl) compared to the control group. The de-creased activity of the four enzymes in liver and one enzymein the kidney of sheep affected by B. decumhens was due tosevere hepatic and kidney damage. Phenobarbitone treat-ment has increased significantly the activity of hepatic en-zymes Cytochrome P,450, UDP glucuronyltransferase(p<O.OOI); Aminopyrine-N -demethylase, Aniline-a-hydroxy-lase (p-dl.Ol ) and Glutathione-s-transferase (p<O.05) com-pared to with the control group. Except for Cytochrome P-450, phenobarbitone has also increased the activity of theabove enzymes in the kidney. Meanwhile, the activity of theabove enzymes in the liver and kidney of sheep treated withphenobarbitone (Group C) was lower compared to Group B.Nevertheless, the activity of hepatic enzymes was still sig-nificantly higher (p<O.OOI) compared to with Group D ani-mals. Our data (Group B and Group C) clearly show thatphenobarbitone is a good inducer of Cytochrome PA50,Aminopyrine-N-demethylase, Aniline-4-hydrozylase, UDPglucuronyltranferase and Glutathione-s-transferase. Induc-tion of these enzymes demonstrated the ability of phenobar-bitone to prevent B. decumbens toxicity in sheep.ConclusionsPhenobarbitone treatment has significantly increased the en-zyme activities in the liver and kidney of sheep in both thegroups. However, the induction of enzyme activities by phe-nobarbitone in group C was slightly lower than in Group B.The increased in enzyme activities especially in the liverprovided some protection to sheep from the toxic effect of B.decumbens in phenobarbitone. Treated sheep than those notgiven as reflected by two out of six rams in Group C devel-oped the toxic signs much later and milder compared to theintoxicated sheep in Group D which were not given pheno-barbitone. The present results suggest that phenobarbitonemay be useful in preventing Signal grass (B. decumbens)toxicity in sheep.ReferencesDutton, GJ. and Storey, I.D.E. 1962. Glucuronide forming enyzmes.In: Method in Enzymology, Vo!' 5, eds. Colowick, S.P. andKaplan, N.D. Academic Press Inc, New Yorfk. p.159-164.Mazel, P. 1971. Experiments illustrating drug metabolism in vitro.In: Fundamental of Drug Metabolism and Drug Disposition, eds.La Du, B.N., Mandel, H.G. and Way, E.L., p. 546-582.Salam Abdullah, A., Nordin, M.M. and Rajion, M.A. 1989. Neuro-logical disorder in sheep during signal grass (Brachiaria decum-bens) toxicity. Vet. Human Toxicol. 31: 128-129.Salam Abdullah, A., Nordin, M.M. and Rajion, M.A., Ragavan, K.and Osman, A. (1994). The use of zinc sulphate for preventingof Brachiaria decumbens (signal grass) toxicity in sheep. Proc.6th Int. Congress European Association Veterinary Pharmacologyand Toxicology 7-11 August, Edinburg, Scotland.Supported by IRPA Grant 01-02-04-0088

The use of enzyme inducers in preventing signal grass (Brachiaria decumbens) toxicity in sheep

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The use of enzyme inducers in preventing signal grass (Brachiaria decumbens) toxicity in sheep

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