Dichloromethane potentiation of carbon tetrachloride hepatotoxicity in rats

Concomitant treatment of rats with a nonhepatotoxic dose of dichloromethane (6 mmol/kg, i.p.) significantly potentiated the hepatotoxicity of carbon tetrachloride (2 mmol/kg, i.p.). Toxicity was determined by increases in serum sorbitol dehydrogenase and alanine aminotransferase activities measured 24 hr following the treatments. Dichloromethane did not affect the lipid peroxidation induced by carbon tetrachloride as determined by conjugated diene formation in hepatic microsomal lipids. The covalent binding of [14C]Cl4 metabolites to microsomal lipids was increased significantly by dichloromethane. The results suggest that dichloromethane potentiates carbon tetrachloride hepatotoxicity by increasing covalent binding of its metabolites to hepatic microsomal lipids.