Liver damage from narcotics in mice

Abstract

Single or multiple intraperitoneal injections of morphine, dihydromorphinone or methadone into mice produced fatty infiltration of the liver and increases of up to 10-fold in the level of serum glutamate-oxaloacetate transaminase (SGOT). Changes in SGOT were proportional to the dose of morphine, and reached a peak at 12–16 hr after injection. Hepatotoxicity was blocked by naloxone and was not seen after dextrorphan, or in animals that had previously been made tolerant to narcotics. Liver damage was more severe in mice kept on pine shavings than in animals kept on corncob bedding. Liver damage was partially blocked by chloramphenicol, but not by SKF-525A. Liver damage was also partially blocked by reserpine and propranolol. Sex and strain differences in susceptibility were observed. The injection of 50–100 μg of morphine sulfate or [ d-Ala 2]-Met-enkephalinamide into the cerebral ventricles produced liver damage comparable to that produced by 50 mg/kg morphine sulfate ip. Both central and peripheral actions of narcotics may be involved in hepatotoxicity.