Effects of methotrexate on antioxidant enzyme status in a rodent model

Abstract

Methotrexate (MTX), a folic acid antagonist is widely used as a cytotoxic chemotherapeutic agent, however its associated hepatotoxicity is considered to be a major clinical side-effect. The aim of this study was to investigate the status of antioxidant enzymes during oxidative stress in liver homogenates of rats subjected to oral methotrexate administration. A total of forty two, 7-week old male Wistar rats with mean weight of 172 g, divided into two groups were used. The first group, control (n = 6), were fed only standard rat chow as their diet and water ad libitum. The second group (n = 36, subdivided into six sub-groups), fed on the same rat chow diet, received orally administered methotrexate at a dose of 13.4 mg/kg at weekly intervals for 6 consecutive weeks. Thiobarbituric acid reactive substance (TBARS) levels and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were subsequently determined spectrophotometrically on liver homogenates of all animals. It was found that methotrexate caused a significant increase in TBARS levels (an important marker of lipid peroxidation) in the methotrexate administered groups when compared with the control group (P < 0.05). The activities of superoxide dismutase, catalase, and glutathione reductase were significantly decreased in the methotrexate groups at weeks 2, 3, 4, 5 and 6 when compared with the control group (P < 0.05). The results therefore indicate that methotrexate causes oxidative stress by reducing the activities and consequently the effectiveness of the antioxidant enzyme defense system.