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.
Freeman, R. W., & Harbison, R. D. (1981). Hepatic periportal necrosis induced by chronic administration of cocaine. Biochemical Pharmacology, 30(7), 777–783. https://doi.org/10.1016/0006-2952(81)90165-9