Therapeutic effects of cimetidine on acetaminophen-induced hepatotoxicity in rats

Acetaminophen is a widely used analgesic and antipyretic drug. An overdose can cause life-threatening hepatotoxicity in humans and experimental animals. In this study, 80 female Sprague–Dawley rats randomized into eight groups (three control and five test groups) were used. Three milligrams per kilogram acetaminophen was administered orally to induce liver necrosis. Cimetidine (12.5 mg/kg) was administered intraperitoneally at 0, 1, 2, 4, and 8 h after acetaminophen administration. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and extent of pathologic changes in liver were evaluated in all groups (1–8), and were found to be increased in group 2 (acetaminophen control), but not in groups 1 and 3 (control groups), and were decreased in some treatment groups. The decrease observed in groups 7 and 8 was more than that in group 6. However, in these groups, more animals died due to toxicity before blood sampling. It was concluded that injection of cimetidine 2 h after acetaminophen administration (group 6) can markedly decrease the serum levels of ALT, AST, and the extent of pathologic lesions in the liver with minimal toxicity and death.