Cocaine was administered intraperitoneally to male mice at doses of 10, 20 or 30 mg/kg daily for 5 days for periods of 1, 2 and 3 weeks. A dose- and time-dependent periportal hepatic necrosis was noted. The extent of hepatic damage varied from vacuolization of hepatocytes to frank necrosis. No drug-related deaths were noted at any of the dosages studied. The hepatic damage elicited by chronic cocaine was found to be of a transient nature. Chronic cocaine treatment elevated serum glutamicpyruvic transminase levels in a dose- and time-dependent manner. Hepatic cytochrome P450levels were depressed significantly in the 30 mg · kg-1· day-1dosage group at 1, 2 and 3 weeks. Hexobarbital-induced narcosis was lengthened significantly in the 30 mg · kg-1· day-1group throughout the course of the study. Chronic administration of cocaine produced a hepatic necrosis that closely resembled that produced by cocaine administered to animals pretreated with stimulators of hepatic metabolism. © 1981.
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