Preventive and curative effect of edaravone on nerve functions and oxidative stress in experimental diabetic neuropathy.
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.
Saini
Anuj Kumar
AK
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar (Mohali), Punjab-160062, India.
Kumar H S
Arun
A
Sharma
Shyam Sunder
SS
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D013979:Tibial Nerve / Q000187:drug effects* / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects
D016166:Free Radical Scavengers; D002374:Catalase; D013482:Superoxide Dismutase; D000077553:Edaravone; D000983:Antipyrine