title: 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 (60mg/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+1mL/kg saline (n=12), Group 3: DM+300mg/kg LEV (n=10), Group 4: DM+600mg/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.
authors.affiliation: Istanbul Bilim University School of Medicine, Department of Physiology, Istanbul, Turkey.
authors.forename: Oytun
authors.initials: O
authors.lastname: Erbaş
authors.affiliation: Ege University School of Medicine, Department of Histology and Embryology, Izmir, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Oltulu
authors.affiliation: Mugla University School of Medicine, Department of Neurology, Mugla, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Yılmaz
authors.affiliation: Ege University School of Medicine, Department of Histology and Embryology, Izmir, Turkey.
authors.forename: Altuğ
authors.initials: A
authors.lastname: Yavaşoğlu
authors.affiliation: Ege University School of Medicine, Department of Physiology, Izmir, Turkey. Electronic address: dilek.taskiran@ege.edu.tr.
authors.forename: Dilek
authors.initials: D
authors.lastname: Taşkıran
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004576:Electromyography; D004594:Electrophysiology; D007124:Immunoenzyme Techniques; D000077287:Levetiracetam; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008054:Lipid Peroxides; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D000077287:Levetiracetam; D053148:Caspase 3; D010889:Piracetam
keywords: Apoptosis; Diabetes mellitus; Diabetic neuropathy; Electromyography; Levetiracetam; Oxidative stress