Neuroprotective effects of chronic administration of levetiracetam in a rat model of diabetic neuropathy

Abstract

Objective: Diabetic neuropathy (DNP) is a frequent and serious complication of diabetes mellitus (DM) that leads to progressive and length-dependent loss of peripheral nerve axons. The purpose of the present study is to assess the neuroprotective effects of levetiracetam (LEV) on DNP in a streptozotocin (STZ)-induced DM model in rats. Methods: Adult Sprague-Dawley rats were administered with STZ (60 mg/kg) to induce diabetes. DNP was confirmed by electromyography (EMG) and motor function test on 21st day following STZ injection. Study groups were assigned as follows; Group 1: Naive control (n = 8), Group 2: DM + 1 mL/kg saline (n = 12), Group 3: DM + 300 mg/kg LEV (n = 10), Group 4: DM + 600 mg/kg LEV (n = 10). LEV was administered i.p. for 30 consecutive days. Then, EMG, motor function test, biochemical analysis (plasma lipid peroxides and total antioxidant capacity), histological and immunohistochemical analysis of sciatic nerves (TUNEL assay, bax, caspase 3, caspase 8 and NGF) were performed to evaluate the efficacy of LEV. Results: Treatment of diabetic rats with LEV significantly attenuated the inflammation and fibrosis in sciatic nerves and prevented electrophysiological alterations. Immunohistochemistry of sciatic nerves showed a considerable increase in bax, caspase 3 and caspase 8 and a decrease in NGF expression in saline-treated rats whereas LEV significantly suppressed apoptosis markers and prevented the reduction in NGF expression. Besides, LEV considerably reduced plasma lipid peroxides and increased total anti-oxidant capacity in diabetic rats. Conclusions: The results of the present study suggest that LEV may have therapeutic effects in DNP through modulation of anti-oxidant and anti-apoptotic pathways. (C) 2016 Elsevier Ireland Ltd. All rights reserved.