title: Effects of trolox on nerve dysfunction, thermal hyperalgesia and oxidative stress in experimental diabetic neuropathy.
abstract: 1. Diabetic neuropathy is one of the most common complications of diabetes and oxidative stress has been implicated to play a major role in its pathophysiology. 2. In the present study, we targeted oxidative stress using trolox, an anti-oxidant, in streptozotocin-induced diabetic neuropathy in rats. 3. Compared with control rats, diabetic rats showed significant deficits in motor nerve conduction velocity (MNCV; 49.91 +/- 1.94 vs 42.77 +/- 1.39 m/s, respectively) and nerve blood flow (NBF; 107.98 +/- 8.22 vs 38.9 +/- 2.7 arbitarary perfusion units, respectively) after 8 weeks of diabetes. Tail flick latencies for cold and hot immersion tests were also significantly reduced in diabetic rats, indicating thermal hyperalgesia. These observations indicate development of diabetic neuropathy. 4. A significant decrease in the activity of anti-oxidant enzymes (superoxide dismutase and catalase) and an increase in lipid peroxidation were observed in sciatic nerves from diabetic rats compared with age-matched control rats. Alterations in the activity of anti-oxidant enzymes and lipid peroxidation in diabetic rats indicate oxidative stress in diabetic neuropathy. 5. Two weeks treatment with trolox (10 and 30 mg/kg, i.p.) started on completion of the 6th week of diabetes significantly improved MNCV, NBF and inhibited thermal hyperalgesia. Trolox treatment also improved the activity of anti-oxidant enzymes and inhibited lipid peroxidation in sciatic nerves of diabetic rats. 6. The results of the present study suggest the beneficial effects of trolox in experimental diabetic neuropathy.
authors.affiliation: Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India. ssharma@niper.ac.in
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Sharma
authors.forename: Sufyan G
authors.initials: SG
authors.lastname: Sayyed
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002374:Catalase / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy*; D015227:Lipid Peroxidation; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000201:enzymology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002839:Chromans; D002374:Catalase; D013482:Superoxide Dismutase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid