Curcumin Ameliorates Methotrexate-Induced Nephrotoxicity in Rats

Methotrexate is an effective anticancer and immunosuppressive agent. However, nephrotoxicity is one of the complications of its use. On the other hand, curcumin, a naturally occurring polyphenolic compound, is reported to have antioxidant and anti-inflammatory properties. Those two properties are likely to prevent methotrexate-induced nephrotoxicity. The aim of this study is to evaluate the possible protective effect of curcumin against methotrexate-induced nephrotoxicity and delineate various mechanism(s) underlies this effect in rats. Nephrotoxicity was induced in Wistar rats by intraperitoneal administration of methotrexate (7 mg/kg/day) for three consecutive days. Curcumin administration in methotrexate-intoxicated rats resulted in nephroprotective effects as evidenced by the significant decrease in levels of serum creatinine and urea as well as renal malondialdehyde, nitric oxide, and tumor necrosis factor-α with a concurrent increase in renal glutathione peroxidase and superoxide dismutase activities compared to nephrotoxic untreated rats. Additionally, immunohistochemical analysis demonstrated that curcumin treatment markedly reduced cyclooxygenase-2 expression. Histopathological examination confirmed the protective effects of curcumin. In conclusion, curcumin protected rats from methotrexate nephrotoxicity, at least in part, through its antioxidant and anti-inflammatory activities.