N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats.

Methotrexate (MTX), a folic acid antagonist, is widely used as a cytotoxic chemotherapeutic agent for malignancies as well as in the treatment of various inflammatory diseases. The efficacy of this agent is often limited by severe side effects and toxic conditions. The present study was undertaken to determine whether N-acetylcysteine (NAC), as a potent antioxidant compound, could ameliorate MTX-induced oxidative liver damage.A single dose of MTX (20 mg/kg, intraperitoneal) to rats was followed by intraperitoneal saline or NAC administration (150 mg/kg, MTX + NAC group) for the next 5 days. On the fifth day the rats were sacrificed and liver tissue samples were obtained and stored to measure reduced glutathione (GSH) and malondialdehyde (MDA) levels and myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity.MTX caused decreased GSH level and SOD and CAT activity and increased MDA level and MPO activity in the liver homogenates. These changes were significantly reversed by NAC treatment.These results confirm that administration of NAC decreases MTX-induced oxidative damage to the liver. These data indicate that NAC may be of therapeutic use in preventing hepatotoxicity in patients receiving MTX treatment.