The role of stimulated lipid peroxidation and impaired calcium sequestration in the enhancement of cocaine induced hepatotoxicity by ethanol

The purpose of this study was to investigate possible mechanism of cocaine- induced hepatotoxicity and its potentiation by ethanol in mice. Ethanol (2 g/kg) and/or cocaine (25 mg/kg) injections were given as binge model (five injections in 3 days). Cocaine administration with or without ethanol cause d an increase in lipid peroxidation in liver homogenate and its subcellular fractions. The greatest increases were observed in mitochondrial fraction following cocaine plus ethanol treatment. Also, glutathione (GSH) levels we re increased in liver homogenate and its mitochondrial fractions after coca ine and cocaine plus ethanol treatment. Microsomal calcium sequestration wa s found to decrease in all treatments. These results suggest that increased lipid peroxidation and decreased microsomal calcium sequestration in the l iver may play a possible role cocaine-induced hepatotoxicity and its potent iation by ethanol. (C) 2000 Elsevier Science Ireland Ltd. All rights reserv ed.