Effects of resveratrol on nerve functions, oxidative stress and DNA fragmentation in experimental diabetic neuropathy.
Oxidative stress has been implicated in pathophysiology of diabetic neuropathy. All the pathways responsible for development of diabetic neuropathy are linked to oxidative stress in one way or the other. In the present study, we have targeted oxidative stress in diabetic neuropathy using resveratrol, a potent antioxidant. Eight weeks streptozotocin-diabetic rats developed neuropathy which was evident from significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and increased thermal hyperalgesia. The 2-week treatment with resveratrol (10 and 20 mg/kg, i.p.) started 6 weeks after diabetes induction significantly ameliorated the alterations in MNCV, NBF, and hyperalgesia. Resveratrol also attenuated enhanced levels of malondialdehyde (MDA), peroxynitrite and produced increase in catalase levels in diabetic rats. There was marked reduction in DNA fragmentation observed after resveratrol treatment in diabetic rats as evident from decrease in Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in sciatic nerve sections. Results of the present study suggest the potential of resveratrol in treatment of diabetic neuropathy and its protective effect may be mediated through reduction in oxidative stress and DNA fragmentation.
Kumar
Ashutosh
A
Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab-160062, India.
Kaundal
Ravinder K
RK
Iyer
Seethalakshmi
S
Sharma
Shyam S
SS
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D053938:DNA Fragmentation / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D000077185:Resveratrol; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013267:Stilbenes / Q000627:therapeutic use*
D000975:Antioxidants; D001786:Blood Glucose; D013267:Stilbenes; D000077185:Resveratrol