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 nerve conduction velocity (NCV), reduced nerve blood flow (NBF), and a variety of metabolic abnormalities in peripheral nerve that have been variously ascribed to hyperglycemia, abnormal fatty acid metabolism, ischemic hypoxia, and/or oxidative stress. Some investigators propose that NCV slowing in experimental DPN can be explained entirely on the basis of nerve energy depletion secondary to reduced NBF. This article reports highly selective effects of administration of the antioxidant DL-alpha-lipoic acid (LA) to streptozotocin-injected diabetic rats. LA improved digital sensory but not sciatic-tibial motor NCV, corrected endoneurial nutritive but not composite NBF, increased the mitochondrial oxidative state without correcting nerve energy depletion, and enhanced the accumulation of polyol pathway intermediates without worsening myo-inositol or taurine depletion. These studies implicate oxidative stress as an important pathophysiological factor in experimental DPN. They reveal complex interrelationships among nerve perfusion, energy metabolism, osmolyte content, conduction velocity, and oxidative stress that may reflect the heterogeneous and compartmentalized composition of peripheral nerve.
Stevens
M J
MJ
Division of Endocrinology and Metabolism, University of Michigan, Ann Arbor 48109-0678, USA. stevensm@umich.edu
Obrosova
I
I
Cao
X
X
Van Huysen
C
C
Greene
D A
DA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000378:metabolism / Q000503:physiopathology*; D004734:Energy Metabolism / Q000187:drug effects; D004798:Enzymes / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010525:Peripheral Nerves / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
D004798:Enzymes; D008063:Thioctic Acid; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D019803:Glutathione Disulfide