Effect of 4-Methylpyrazole for Acetaminophen Hepatotoxicity in a Rat Model

ABSTRACT

BACKGROUND: Hepatic necrosis after acetaminophen overdose results from the increased formation of a highly toxic intermediatc(N-acetyl-p-benzoquinoneimine), produced by acetaminophen metabolism through the cytochrome P450 mixed function oxidase system. N-acetyl-p-benzoquinoneimine is normally detoxified by endogenous glutathione, but the increased production induced by an acetaminophen overdose may depletc glutathione stores, allowing the intermediate to react with and to destroy hepatocytes. METHOD & MATERIAL: We have estimated the hepatoprotective effects of 4-methylpyrazole(500mg/kg and 50mg/kg), inhibitor of cytochrone P450 isoenzyme, when given at two hours after single oral overdose of acetaminophen(2,000mg/kg) in rats. RESULTS: As far as overall protective effect of 4-methylpyrazole on hepatic necrosis score concerned, seam transaminase(AST, ALT) level were found to be decreased in 4-methylpyrazole-treated group compared to untreated group after acetaminophen overdose. No consistent difference in hepatoprotective effect was demonstrated between rats with high dose of 4-methylpyazole(500mg/kg) and rats with lower dose of 4-methylpyrazole(50mg/kg). CONCLUSION: We concluded that oral administration of 4-methylpyrazole apperas to protect hepatotoxicity effectively to acetaminophen overdose.