Oral cocaine produces dose-related hepatotoxicity in male mice

Cocaine remains a widely abused substance. While most addicts take cocaine intranasally, a considerable number abuse cocaine by mouth. It has been ass umed that after oral exposure cocaine is hydrolyzed in the stomach renderin g it ineffective. This study investigated the effect of orally administered cocaine on liver function and integrity as well as its effect on liver and blood antioxidative enzymes. Male CF-I mice were orally administered eithe r 0, 5, 10 or 20 mg cocaine/kg body weight and sacrificed 24 h after the la st treatment. Serum alanine aminotransferase (ALT) and aspartate aminotrans ferase (AST) were measured as markers of liver injury. Blood and liver glut athione (GSH) levels were determined as well as the activities of glutathio ne peroxidase (GPx) and catalase (CAT). In addition, the activity of liver glutathione reductase (GRx) was also measured. The results demonstrated tha t oral cocaine caused hepatotoxicity in a dose dependent manner. Serum ALT and AST were elevated while blood GSH concentration decreased in all cocain e treated animals. In addition, there was a significant dose dependent decr ease in the activities of GPx and CAT in blood and liver of cocaine treated animals. However, hepatic GSH content and GRx activity manifested a signif icant increase, particularly in the group, which received 20 mg/kg cocaine. This study is the first to demonstrate that cocaine-induced hepatotoxicity results following the oral route of administration. (C) 2001 Elsevier Scie nce Ireland Ltd. All rights reserved.