Therapeutic effect of cimetidine on acetaminophen-induced nephrotoxicity in rabbits

Acetaminophen is an analgesic and antipyretic drug that can cause nephrotoxicity in humans and experimental animals. Cimetidine is an H₂ blocker used for suppression of gastric acid secretion. One of its side effects is blockade of the cytochrome P-450 enzyme system which results in an increased half-life of some drugs. In this study, 120 female rabbits were randomized into 12 groups (three control and nine test groups). The LD₅₀ of acetaminophen was calculated to be 3.24 g/kg, and a suspension at this concentration was administered orally to induce renal necrosis. Three treatment groups received a single dose of cimetidine (40 mg/kg) administered intravenously at 0, 2, or 4 h after administration of acetaminophen depending upon treatment group. The six remaining treatment groups received cimetidine in two equal doses of 20 mg/kg administered at 0 and 12 h, 0 and 24 h, 2 and 12 h, 2 and 24 h, 4 and 12 h, or 4 and 24 h after the administration of acetaminophen. Blood samples were collected at 0, 12, 24, and 36 h after the induction of acetaminophen toxicity. Blood urea nitrogen and creatinine levels were measured in all groups and were significantly raised in the acetaminophen control group and some treatment groups (p < 0.05). The results indicate that the most effective treatment with cimetidine was obtained with a single dose of cimetidine administered 2 h after acetaminophen intake.