The Influence of Ethanol Pretreatment on the Effects of Nine Hepatotoxic Agents

Abstract

The hepatotoxic effects of CCl4 (0.01 ml/kg, i.p.), thioacetamide (50 mg/kg, i.p.), paracetamol (0.5 g/kg, i.p.) and allyl alcohol (0.05 ml/kg i.p.) as estimated by determination of serum enzyme activities (GOT [glutamic oxalacetic transaminase], GPT [glutamic pyruvic transaminase], SDH [succinic dehydrogenase]) were enhanced in mice treated with 1 oral dose of 4.8 g/kg ethanol 16 h previously. Pretreatment of mice with ethanol did not increase the hepatotoxic actions of bromobenzene (0.25 ml/kg, i.p.), phalloidin (1.5 mg/kg, i.p.), .alpha.-amanitin (0.75 mg/kg, i.p.) and praseodymium (12 mg/kg i.v.), although there was a trend to higher enzyme activities in the case of bromobenzene. In guinea pigs ethanol also aggravated CCl4-induced liver damage, but only strengthened the hepatotoxic activity of D-galactosamine (150 mg/kg, i.p.). Treatment with 4.8 g/kg ethanol did not influence liver glutathione levels in mice, but increased aniline hydroxylation in the 9000 .times. g liver homogenate supernatant of mice and guinea pigs. A dose of 2.4 g/kg ethanol neither increased aniline hydroxylase activity nor enhanced CCl4-induced hepatotoxicity in mice. The enhanced sensitivity to hepatotoxic agents after treatment with ethanol may be due to an enhanced microsomal activation of these substances.