Exacerbation of Acetaminophen Hepatotoxicity by the Anthelmentic Drug Fenbendazole

摘要: Fenbendazole is a broad-spectrum anthelmintic drug widely used to prevent or treat nematode infections in laboratory rodent colonies. Potential interactions between fenbendazole and hepatotoxicants such as acetaminophen are unknown, this was investigated study. Mice were fed control diet containing (8-12 mg/kg/day) for 7 days prior treatment with (300 mg/kg) phosphate buffered saline. In mice diet, administration resulted centrilobular hepatic necrosis increases serum transaminases, which evident within 12 h. Acetaminophen-induced hepatotoxicity markedly increased the fenbendazole-containing measured histologically by significant transaminase levels. Moreover, but not 63% mortality observed 24 h of administration. itself had no effect on liver histology transaminases. To determine if exaggerated due alterations metabolism, we analyzed sera presence free acetaminophen-glucuronide. We found that there differences turnover. also cytochrome P450 (cyp) 2e1, cyp3a, cyp1a2 activity. Whereas activity cyp2e1 suppressed. A prolonged suppression glutathione (GSH) acetaminophen-treated when compared diet. These data demonstrate exacerbates acetaminophen, an related persistent GSH depletion. findings novel suggest potential drug-drug interaction should be considered experimental protocols evaluating mechanisms colonies treated fenbendazole.