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 assumed that after oral exposure cocaine is hydrolyzed in the stomach rendering 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-1 mice were orally administered either 0, 5, 10 or 20 mg cocaine/kg body weight and sacrificed 24 h after the last treatment. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured as markers of liver injury. Blood and liver glutathione (GSH) levels were determined as well as the activities of glutathione peroxidase (GPx) and catalase (CAT). In addition, the activity of liver glutathione reductase (GRx) was also measured. The results demonstrated that oral cocaine caused hepatotoxicity in a dose dependent manner. Serum ALT and AST were elevated while blood GSH concentration decreased in all cocaine treated animals. In addition, there was a significant dose dependent decrease in the activities of GPx and CAT in blood and liver of cocaine treated animals. However, hepatic GSH content and GRx activity manifested a significant 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.
Labib
R
R
Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2714, USA.
Turkall
R
R
Abdel-Rahman
M S
MS
D000284:Administration, Oral; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D013482:Superoxide Dismutase / Q000378:metabolism
D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D003042:Cocaine