Glutathione and alpha-lipoate in diabetic rats: nerve function, blood flowand oxidative state

Background Increased oxidative stress is considered to be a causal factor i n the development of diabetic complications, among which peripheral neuropa thy. The pathophysiology of nerve dysfunction in diabetes has been explaine d both by reduced endoneurial microcirculation and alterations in endoneuri al metabolism. It is unclear whether antioxidants primarily improve nerve b lood flow or normalise systemic or endoneurial oxidative metabolism. Theref ore, we evaluated the effects of the antioxidants glutathione and alpha -li poic acid on both nerve microcirculation and the antioxidative capacity and lipid peroxidation in experimentally diabetic rats. Materials and Methods Streptozotocin-diabetic rats were treated with differ ent doses of alpha -lipoic acid, reduced glutathione or placebo, and were c ompared with nondiabetic controls. We measured systemic and endoneurial ant ioxidants, malondialdehyde and whole blood hydrogen peroxide. Furthermore, we evaluated sciatic and tibial motor and sensory nerve conduction velocity , caudal nerve conduction velocity, and assessed sciatic nerve blood flow a nd vascular resistance by Laser-Doppler flowmetry Results We observed a rise in erythrocyte glutathione by 27% (P < 0.05), an d a trend towards decreased plasma malondialdehyde in <alpha>-lipoic acid, but not in glutathione-treated animals in comparison with the placebo group . Simultaneously, sciatic nerve blood now and vascular resistance were impr oved by daily alpha -lipoic acid administration by 38% (P < 0.05). Peripher al nerve conduction velocity and endoneurial glutathione were not significa ntly influenced by antioxidant treatment. Conclusions Only minor beneficial effects of <alpha>-lipoic acid on nerve b lood flow and oxidative state occur at the given doses; these effects were insufficient to improve nerve conduction deficits.