ALPHA-LIPOIC ACID - ANTIOXIDANT POTENCY AGAINST LIPID-PEROXIDATION OFNEURAL TISSUES IN-VITRO AND IMPLICATIONS FOR DIABETIC NEUROPATHY

Nerve lipid peroxidation is increased in experimental diabetic neuropa thy, and alpha-lipoic acid will prevent the deficits in nerve blood fl ow, oxidative stress, and distal sensory conduction. Because these alt erations can occur by mechanisms other than augmenting lipid peroxidat ion in vivo, and because both pro-oxidant and antioxidant effects of t he agent have been reported, we undertook studies of in vitro lipid pe roxidation of brain and sciatic nerve using an in vitro lipid peroxida tion model with an ascorbate-iron-EDTA system. We evaluated the effect iveness of the R(+)-, S(-)-enantiomers, and racemate of alpha-lipoic a cid in reducing thiobarbituric acid reactive substances (TEARS) genera tion in rat brain and sciatic nerve. Studies were also done in an incu bation medium containing 20 mM glucose, which increased lipid peroxida tion up to fourfold. A dose-dependent and statistically significant re duction in lipid peroxidation was seen with both tissues with similar potencies for both enantiomers. This effect was unassociated with any reduction in the loss of alpha-tocopherol.