Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart

Abstract

Objective: Methotrexate (MTX), an antifolate and antimetabolite, is used in the treatment of cancer and autoimmune diseases, however, it can cause many adverse events. Lipoic acid (LA) has anticancer and antioxidant activities, and due to these properties, it is effective in curing the complications of various disorders. The study aims to investigate the potential therapeutic effect of LA on MTX-induced oxidative stress in the heart tissues of rats. Materials and Methods: Eighteen Wistar Albino rats were divided equally into 3 groups as follows: Controls, MT group (MTX was injected with a single dose of 20 mg/kg, i.p.) and MT+LA group (MTX was injected with a single dose of 20 mg/kg, i.p. on the first day and LA (dissolved in saline, 50 mg/kg/day, i.p,) was injected for 5 days). On the sixth day, rats were sacrificed under general anesthesia. Total protein, lipid peroxidation (LPO), nitric oxide (NO), sialic acid (SA), and glutathione (GSH) levels, and also catalase (CAT), superoxide dismutase (SOD) and glutathione-s-transferase (GST) activities were determined in 10% (w/v) heart homogenates. Results: MTX administration significantly increased LPO and NO levels, and SOD activity and significantly decreased GSH level and CAT activity. LA reversed these parameters by decreasing LPO and NO levels and SOD activity, and increasing GSH levels significantly. Conclusion: LA has beneficial effects on the impaired oxidant/antioxidant status and is effective in reducing oxidative stress during MTX administration in the heart tissue of rats. Keywords: Methotrexate, lipoic acid, oxidative stress, heart, rat