Therapeutic effect of cimetidine on acetaminophen-induced nephrotoxicity in rats

Acetaminophen as an analgesic and antipyretic drug can induce renal toxicity in high doses. Cimetidine as an H₂-blocker can inhibit the cytochrome P450 enzymes and reduce the toxic effect of acetaminophen on renal tissue. Eighty rats in eight groups comprising normal control group, acetaminophen control group, cimetidine control group, and five different treatment groups (cimetidine was administrated at 0, 1, 2, 4, and 8 h after acetaminophen administration) were used. Acetaminophen was administered at a toxic of dose 3 g/kg orally, and cimetidine (12.5 mg/kg) was administrated by intraperitoneal route at different times after induction of toxicity. Creatinine and urea were measured, and pathologic lesions were determined. In treatment groups 3 and 6, the urea and creatinine concentration showed no significant difference from group 1. In other treatment groups, the urea and creatinine concentrations were increased significantly (p < 0.05). Histopathologic changes in group 6 were mild in comparison to other groups. We concluded that administration of cimetidine at least 2 h after acetaminophen toxicity can reduce renal lesions.