Effects of N-acetylcysteine on methotrexate-induced small intestinal damage in rats

Methotrexate (MTX) is known to cause damage to the small intestine, leading to its dysfunction. The aim of the present study was to examine whether the administration of N-acetylcysteine (NAC) provides protection against the MTX-induced damage to small intestinal epithelium in rats. A single dose of MTX (20 mg/kg, intraperitoneal) was followed by intraperitoneal saline or NAC administration (150 mg/kg, MTX+NAC group) for the next 5 days. Afterward, the rats were sacrificed and small intestinal segments were fixed for light microscopic examinations. Glutathione and malondialdehyde levels, myeloperoxidase, superoxide dismutase and catalase activities were measured in the other intestinal segments. MTX caused an increase in the levels of glutathione and malondialdehyde and in the activities of myeloperoxidase, superoxide dismutase and catalase. These changes were significantly reversed in MTX+NAC-treated rats. Light microscopy in the MTX group revealed mucosal damage, which decreased with NAC treatment. Our results confirmed that administration of NAC decreased the MTX-induced damage to the small intestine. This protective effect of NAC may have clinical applications in chemotherapy.