Beneficial effect of nitric oxide synthase inhibitor on hepatotoxicity induced by allyl alcohol.
The effect of aminoguanidine (a selective inhibitor of inducible nitric oxide synthase) on allyl alcohol-induced liver injury was assessed by the measurement of serum ALT and AST activities and histopathological examination. When aminoguanidine (50-300 mg/kg, i.p.) was administered to mice 30 min before a toxic dose of allyl alcohol (75 microL/kg, i.p.), significant changes related to liver injury were observed. In the presence of aminoguanidine the level of ALT and AST enzymes were significantly decreased. All symptoms of liver necrosis produced by allyl alcohol toxicity almost completely disappeared when animals were pretreated with aminoguanidine at 300 mg/kg. Depletion of hepatic glutathione as a consequence of allyl alcohol metabolism was minimal in mice pretreated with aminoguanidine at 300 mg/kg. It was found that the inhibition of toxicity was not due to alteration in allyl alcohol metabolism since aminoguanidine did not effect alcohol dehydrogenase activity both in vivo and in vitro.
Alam
K
K
Department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, Aligarh, India. kalam786@rediffmail.com
Nagi
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MN
Al-Shabanah
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OA
Al-Bekairi
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AM
D000410:Alanine Transaminase / Q000037:antagonists & inhibitors; D000818:Animals; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D020005:Propanols / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D006146:Guanidines; D020005:Propanols; C006463:allyl alcohol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C004479:pimagedine