Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy

Experimental diabetic peripheral neuropathy (DPN) is marked by impaired ner ve conduction velocity (NCV), reduced nerve blood from (NBF), and a variety of metabolic abnormalities in peripheral nerve that have been variously as cribed to hyperglycemia, abnormal fatty acid metabolism, ischemic hypoxia, and/or oxidative stress. Some investigators propose that NCV slowing in exp erimental DPN can be explained entirely on the basis of nerve energy deplet ion secondary to reduced NBF. This article reports highly selective effects of administration of the antioxidant DL-alpha-lipoic acid (LA) to streptoz otocin-injected diabetic rats. LA improved digital sensory but not sciatic- tibial motor NCV, corrected endometrial nutritive but not composite NBF, in creased the mitochondrial oxidative state without correcting nerve energy d epletion, and enhanced the accumulation of polyol pathway intermediates wit hout worsening myo-inositol or taurine depletion. These studies implicate o xidative stress as an important pathophysiological factor in experimental D PN. They reveal complex interrelationships among nerve perfusion, energy me tabolism, osmolyte content, conduction velocity, and oxidative stress that may reflect the heterogeneous and compartmentalized composition of peripher al nerve.