Effects of trolox on nerve dysfunction, thermal hyperalgesia and oxidative stress in experimental diabetic neuropathy.
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.
Sharma
Shyam S
SS
Molecular Neuropharmacology Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India. ssharma@niper.ac.in
Sayyed
Sufyan G
SG
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
D001786:Blood Glucose; D002839:Chromans; D002374:Catalase; D013482:Superoxide Dismutase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid