Enhanced hepatotoxicity of aflatoxin B1 by pretreatment of rats with ethanol

Hepatotoxicity of aflatoxin B1 (2.0 and 4.0 mg/kg i.p.) as determined by plasma enzyme activities (GPT and GOT), liver triglycerides and histopathologic changes was enhanced in rats pretreated with four oral doses of ethanol (4.0 g/kg each) at 48, 45, 24 and 21 hrs prior to aflatoxin B1 administration. Pretreatment with ethanol (4.0 g/kg) slightly increased liver weight without changing hepatic microsomal protein contents. Also it caused an increase in microsomal aniline hydroxylase but a decrease in p-nitroanisole-o-demethylase, 48 hrs after the first ethanol dose. In the rats pretreated with ethanol, aflatoxin B1 was metabolized at a higher extent to aflatoxins M1 and Q1. These results suggest that an increased hepatotoxicity of aflatoxin B1 after pretreatment with ethanol may presumably due to an increase in microsomal formation of active aflatoxin B1 metabolite.