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

Eur J Clin Invest. 2001 May;31(5):417-24. doi: 10.1046/j.1365-2362.2001.00832.x.

Abstract

Background: Increased oxidative stress is considered to be a causal factor in the development of diabetic complications, among which peripheral neuropathy. The pathophysiology of nerve dysfunction in diabetes has been explained both by reduced endoneurial microcirculation and alterations in endoneurial metabolism. It is unclear whether antioxidants primarily improve nerve blood flow or normalise systemic or endoneurial oxidative metabolism. Therefore, we evaluated the effects of the antioxidants glutathione and alpha-lipoic 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 different doses of alpha-lipoic acid, reduced glutathione or placebo, and were compared with nondiabetic controls. We measured systemic and endoneurial antioxidants, 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 and vascular resistance by Laser-Doppler flowmetry.

Results: We observed a rise in erythrocyte glutathione by 27 % (P < 0.05), and 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 flow and vascular resistance were improved by daily alpha-lipoic acid administration by 38% (P < 0.05). Peripheral nerve conduction velocity and endoneurial glutathione were not significantly influenced by antioxidant treatment.

Conclusions: Only minor beneficial effects of alpha-lipoic acid on nerve blood flow and oxidative state occur at the given doses; these effects were insufficient to improve nerve conduction deficits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Blood Flow Velocity / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / metabolism*
  • Diabetic Neuropathies / physiopathology*
  • Glutathione / administration & dosage
  • Glutathione / metabolism*
  • Injections, Intraperitoneal
  • Male
  • Microcirculation / drug effects
  • Microcirculation / physiopathology
  • Neural Conduction / drug effects
  • Oxidative Stress* / drug effects
  • Peripheral Nerves / blood supply*
  • Peripheral Nerves / drug effects
  • Peripheral Nerves / physiopathology*
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / blood supply
  • Thioctic Acid / administration & dosage
  • Thioctic Acid / metabolism*
  • Tibial Nerve / blood supply
  • Vascular Resistance / drug effects

Substances

  • Antioxidants
  • Thioctic Acid
  • Glutathione