Acetaminophen is an analgesic and antipyretic drug, its overdose cause hepatotoxicity. The
current antidote for acetaminophen hepatotoxicity is N-acetyl cysteine (NAC); however, NAC has
been resulted in severe side effects as seizures, intracranial hypertension and cerebral edema. This
study aimed to assess and compare the ameliorative effects of cimetidine and silymarin against acute
acetaminophen–induced hepatotoxicity. Fifty four adult albino rats were divided into nine groups:
negative control; solvent control; silymarin control; cimetidine control; cimetidine and silymarin
control; acetaminophen group; acetaminophen and silymarin group; acetaminophen and cimetidine
group; acetaminophen, cimetidine and silymarin group. A single dose of: acetaminophen (800 mg/kg,
orally); silymarin (150mg/kg, orally) and cimetidine (150 mg/kg, intraperitoneally) were given
according to study regimen. Liver histopathology, biochemical analysis of liver aminotransferases
(AST & ALT) and hepatic tissue levels of oxidative stress index (MDA) and antioxidant (GSH) were
assessed. Treatment with cimetidine alone gave better biochemical results as compared to treatment
with silymarin alone. However combined treatment with cimetidine and silymarin showed better
ameliorative effects than either of them given alone, evidenced by better improvement in
histopathological examination and biochemical results as compared to other tested groups, and these
results were non-significant as compared to controls. In conclusion treatment with silymarin and
cimetidine in-combination for acute acetaminophen–induced hepatotoxicity showed better
improvement probably due to synergistic hepatoprotective effects.