Ameliorative effects of edaravone against valproic acid-induced kidney damage

Abstract

Valproic acid (VPA) is a well-known and increasingly documented antiepileptic drug that has been widely used in the treatment of epilepsy and/or epilepsy-related disorders. Prolonged clinical use of VPA has been reported to cause side effects such as nephrotoxicity. Edaravone (EDA) is a powerful free radical scavenger. The aim of the study was to investigate the protective effects of EDA against VPA-induced oxidative renal injury. Four experimental groups were formed by randomly assigning thirty-eight male Sprague Dawley rats. The first group, (Control Group, n = 8), consisted of healthy rats. The second group, (Group II, n = 10), comprised control rats given intraperitoneally EDA (30 mg/kg/day) for seven days. The third group (Group III, n = 10) was administered intraperitoneally only VPA (500 mg/kg/day) for seven days. The last group (Group IV, n = 10) was treated with VPA + EDA for seven days. On the 8th day, kidney tissues were immediately removed from rats. In kidney homogenates, reduced glutathione levels and Na/K+-ATPase, paraoxonase1 and prolidase activities were remarkably decreased while catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, myeloperoxidase, and xanthine oxidase activities and lipid peroxidation, protein carbonyl, advanced oxidized protein products, and hydroxyproline contents were notably elevated in VPA given group. Consistently, administration of EDA decreased renal degenerative changes seen in the kidney tissue of VPA given rats. Treatment with EDA in the VPA group significantly resulted in the recovery of both biochemical and histopathological alterations. As a result, EDA is potentially beneficial to revert oxidative renal damage induced by VPA.