Neuroprotective effects of chronic administration of levetiracetam in a rat model of diabetic neuropathy. (April 2016)

• Record Type: Journal Article
• Authors: Erbaş, Oytun; Oltulu, Fatih; Yılmaz, Mustafa; Yavaşoğlu, Altuğ; Taşkıran, Dilek
• Is Part Of: Diabetes research and clinical practice. Volume 114(2016)
• Page Start: 106
• Page End: 116
• Publication Date: 2016-04
• Subjects: Diabetes mellitus -- Diabetic neuropathy -- Levetiracetam -- Oxidative stress -- Electromyography -- Apoptosis; Diabetes -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462
• DOI: 10.1016/j.diabres.2015.12.016
• Languages: English
• ISSNs: 0168-8227

Abstract

Highlights: Efficacy of levetiracetam (LEV) in diabetic neuropathy was evaluated in a rat model. LEV significantly prevented electrophysiological alterations in diabetes group. LEV significantly suppressed apoptosis and prevented the decrease in NGF expression. LEV reduced lipid peroxides and increased anti-oxidant capacity in diabetic rats. These finding suggest that LEV may have beneficial effects in 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: Naïve 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 anti-oxidant 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.