Preventive and curative effect of edaravone on nerve functions and oxidative stress in experimental diabetic neuropathy

Eur J Pharmacol. 2007 Jul 30;568(1-3):164-72. doi: 10.1016/j.ejphar.2007.04.016. Epub 2007 Apr 22.

Abstract

Oxidative stress is implicated as a final common pathway in the development of diabetic neuropathy and pharmacological interventions targeted at inhibiting free radical production have shown beneficial effects. In the present study, we have investigated the effects of edaravone (3 mg/kg; 3-Methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger (relatively selective to hydroxyl radicals) in streptozotocin (50 mg/kg i.p.) induced diabetic neuropathy in male Sprague-Dawley rats. Significant reduction (18%) in motor nerve conduction velocity, nerve blood flow (55%) and tail flick latency in cold (53%) and hot (50%) immersion test was observed in diabetic rats compared to age matched non-diabetic rats. Preventive (8 week) and curative (2 week) treatment of edaravone significantly improved the nerve conduction velocity and nociception but not nerve blood flow in diabetic rats. The changes in lipid peroxidation status and anti-oxidant enzymes (Superoxide dismutase and Catalase) levels observed in diabetic rats were significantly restored by edaravone treatment. Increase in blood pressure and vascular resistance was also significantly attenuated by edaravone treatment. This study provides experimental evidence to preventive and curative effect of edaravone on nerve function and oxidative stress in animal model of diabetic neuropathy. Hence edaravone may be tried clinically for the treatment of diabetic neuropathy since it is clinically used in stroke patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipyrine / analogs & derivatives*
  • Antipyrine / therapeutic use
  • Catalase / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / physiopathology
  • Edaravone
  • Free Radical Scavengers / therapeutic use*
  • Lipid Peroxidation / drug effects
  • Male
  • Neural Conduction / drug effects
  • Oxidative Stress / drug effects
  • Pain / drug therapy
  • Pain / metabolism
  • Pain / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / drug effects
  • Sciatic Nerve / blood supply
  • Sciatic Nerve / drug effects*
  • Sciatic Nerve / physiology
  • Superoxide Dismutase / metabolism
  • Tibial Nerve / drug effects*
  • Tibial Nerve / physiology
  • Vascular Resistance / drug effects

Substances

  • Free Radical Scavengers
  • Catalase
  • Superoxide Dismutase
  • Edaravone
  • Antipyrine