Ameliorative Effect of Gallic Acid on Methotrexate-Induced Hepatotoxicity and Nephrotoxicity in Rat.

Abstract

We investigated the protective effect of gallic acid (GA) against methotrexate (MTX)-induced hepatotoxicity and nephrotoxicity. Male Wistar rats were randomized into five groups (n = 6/group): I, control; II, MTX-treated for seven days; III, pre-treated with GA for seven days, followed by MTX for seven days; IV, co-treated with MTX and GA for seven days and V, GA for seven days. MTX caused a significant increase (P<0.05) in plasma biomarkers of nephrotoxicity (urea, creatinine) and hepatotoxicity (Bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase) when compared with control. Furthermore, MTX caused a significant decrease in the activities of hepatic enzymic antioxidants (superoxide dismutase, catalase, glutathione S-transferase) and nonenzymic antioxidants (Vitamin C and glutathione), followed by a significant increase in hepatic malondialdehyde content. However, pre-treatment and co-treatment with gallic acid ameliorated the MTX-induced biochemical changes observed. Taken together, GA protected against MTX-induced hepatotoxicity and nephrotoxicity in rats, by reducing the impact of oxidative damage to tissues.