THE ROLES OF OXIDATIVE STRESS AND ANTIOXIDANT TREATMENT IN EXPERIMENTAL DIABETIC NEUROPATHY

Oxidative stress is present in the diabetic state, Our work has focuse d on its presence in peripheral nerves, Antioxidant enzymes are reduce d in peripheral nerves and are further reduced in diabetic nerves, Tha t lipid peroxidation will cause neuropathy is supported by evidence of the development of neuropathy Be novo when normal nerves are rendered alpha-tocopherol deficient and by the augmentation of the conduction deficit in diabetic nerves subjected to this insult, Oxidative stress appears to be primarily due to the processes of nerve ischemia and hyp erglycemia auto-oxidation. The indexes of oxidative stress include an increase in nerve, dorsal root, and sympathetic ganglia lipid hydroper oxides and conjugated dienes. The: most reliable and sensitive index, however is a reduction in reduced glutathione, Experimental diabetic n europathy results in myelinopathy of dorsal roots and a vacuolar neuro pathy of dorsal root ganglion. The vacuoles are mitochondrial; we posi t that lipid peroxidation causes mitochondrial DNA mutations that incr ease reduced oxygen species, causing further damage to mitochondrial r espiratory chain and function and resulting in a sensory neuropathy, a lpha-lipoic acid is a potent antioxidant that prevents Lipid peroxidat ion in vitro and in vivo, We evaluated the efficacy of the drug in dos es of 20, 50, and 100 mg/kg administered intraperitoneally in preventi ng the biochemical, electrophysiological, and nerve blood flow deficit s in the peripheral nerves of experimental diabetic neuropathy, alpha- lipoic acid dose- and time-dependently prevented the deficits in nerve conduction and nerve blood flow and biochemical abnormalities (reduct ions in reduced glutathione and lipid peroxidation), The nerve blood f low deficit was 50% (P < 0.001), Supplementation dose-dependently prev ented the deficit; at the highest concentration, nerve blood flow was not different from that of control nerves, Digital nerve conduction un derwent; a dose-dependent improvement at 1 month (P < 0.05), By 3 mont hs, all treated groups had lost their deficit, The antioxidant drug is potentially efficacious for human diabetic sensory neuropathy.