Anti-oxidant and pro-oxidant effects on nerve conduction velocity, endoneurial blood flow and oxygen tension in non-diabetic and streptozotocin-diabetic rats

Diabetologia. 1994 May;37(5):449-59. doi: 10.1007/s001250050131.

Abstract

Increased oxygen free radical activity, coupled with reduced protection against oxidative stress, could play a role in the aetiology of neurovascular abnormalities in experimental diabetes mellitus. To test this hypothesis, non-diabetic and streptozotocin-diabetic rats were treated with the anti-oxidant probucol or the pro-oxidant primaquine. One-month diabetes caused 21.4% and 13.6% reduction in sciatic motor and saphenous sensory conduction velocity (p < 0.001). These deficits were prevented by probucol treatment (p < 0.001). After 1-month untreated diabetes, conduction velocity deficits were reversed by a further month of probucol treatment (p < 0.001). For non-diabetic rats, primaquine treatment caused a 12.9% reduction in motor conduction velocity (p < 0.001), which was prevented by probucol treatment (p < 0.001). Primaquine treatment did not affect diabetic rats. Sciatic nerve nutritive endoneurial blood flow, measured using microelectrode polarography and hydrogen clearance, was 48.0% reduced by 2-month diabetes (p < 0.001). This was completely prevented by probucol treatment (p < 0.001). Primaquine treatment did not affect blood flow in diabetic rats. However, in non-diabetic rats it caused a 30.0% reduction (p < 0.01) which was prevented by probucol treatment (p < 0.05). Sciatic endoneurial oxygen tensions were also measured by microelectrode polarography. Mean tension was 38.8% reduced by diabetes (p < 0.001). This was prevented by probucol treatment. Non-diabetic rats given primaquine treatment showed a 21.7% reduction in endoneurial oxygen tension (p < 0.01). The data suggest that vascular-mediated nerve dysfunction in diabetes depends on oxidative stress, and that similar effects in non-diabetic rats may be produced by pro-oxidant treatment. This provides evidence for the potentially important role of oxygen free radical activity in diabetic neuropathy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / physiopathology*
  • Inositol / metabolism
  • Male
  • Motor Neurons / drug effects
  • Motor Neurons / physiology
  • Neural Conduction / drug effects
  • Neural Conduction / physiology*
  • Oxygen / analysis
  • Peripheral Nerves / blood supply
  • Peripheral Nerves / drug effects
  • Peripheral Nerves / physiopathology*
  • Polarography
  • Primaquine / pharmacology*
  • Probucol / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reference Values
  • Regional Blood Flow / drug effects
  • Sciatic Nerve / blood supply
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / physiopathology*
  • Sugar Alcohols / metabolism

Substances

  • Blood Glucose
  • Sugar Alcohols
  • Inositol
  • Primaquine
  • Probucol
  • Oxygen