Alpha-lipoic acid: antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy.
Nerve lipid peroxidation is increased in experimental diabetic neuropathy, and alpha-lipoic acid will prevent the deficits in nerve blood flow, oxidative stress, and distal sensory conduction. Because these alterations can occur by mechanisms other than augmenting lipid peroxidation in vivo, and because both pro-oxidant and antioxidant effects of the agent have been reported, we undertook studies of in vitro lipid peroxidation of brain and sciatic nerve using an in vitro lipid peroxidation model with an ascorbate-iron-EDTA system. We evaluated the effectiveness of the R(+)-, S(-)-enantiomers, and racemate of alpha-lipoic acid in reducing thiobarbituric acid reactive substances (TBARS) generation in rat brain and sciatic nerve. Studies were also done in an incubation medium containing 20 mM glucose, which increased lipid peroxidation up to fourfold. A dose-dependent and statistically significant reduction 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.
Department of Neurology, Mayo Foundation, Rochester, MN 55905, USA.
K K
KK
Nickander
B R
BR
McPhee
P A
PA
Low
H
H
Tritschler
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009417:Nerve Tissue / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D008063:Thioctic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014810:Vitamin E / Q000378:metabolism
D000975:Antioxidants; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D008063:Thioctic Acid