Cocaine-induced hepatotoxicity: lipid peroxidation as a possible mechanism

In vitro experiments with hepatic washed microsomal preparations showed that malondialdehyde (MDA) formation was increased in a time- and concentration-dependent manner using COC or NC as the substrate. Though 1 mM COC or NC inhibited MDA formation, significant elevations were observed for 100, 10 or 1 microM concentrations. NC at 10 microM after a 30 minute incubation produced a 34% decrease in hepatic microsomal cytochrome P450 whereas 1 mM NC had no such effect. MDA formation in vivo, measured as total absorbance at 535 nm per gram liver, was found to be maximal 4 hours after 40 mg/kg NC ip. Elevations of serum transaminase (SGPT) however were not found until 6 hours after NC. We conclude from these studies that COC and NC induce lipid peroxidation in the liver of PB-pretreated Swiss-origin mice and that peroxidative attack may be a mechanism for hepatotoxicity of these compounds.