Anti-oxidant treatment prevents the development of peripheral nerve dysfunction in streptozotocin-diabetic rats

Diabetologia. 1993 Apr;36(4):299-304. doi: 10.1007/BF00400231.


We tested the notion that oxidative stress makes an important contribution to the aetiology of diabetic neuropathy. The effect of treatment with a 1% dietary supplement of the anti-oxidant butylated hydroxytoluene was studied during 2 months of streptozotocin-induced diabetes mellitus. In final experiments, sciatic motor and saphenous sensory conduction velocities were measured in vivo, and resistance to hypoxic conduction failure for sciatic trunk was examined in vitro. There were 20% and 12% decreases in motor and sensory conduction velocity, respectively after 2 months of diabetes (p < 0.001). There were completely prevented by butylated hydroxytoluene treatment (p < 0.001). Resistance to hypoxic conduction failure, shown by the time taken for sciatic compound action potential amplitude to decline by 80%, was 55% increased by diabetes, and this was limited to 31% (p < 0.01) by treatment. There were no significant effects of treatment on the 9-10 fold elevation of sciatic nerve sorbitol and fructose levels with diabetes, or on the non-significant 22% reduction in myoinositol content. Butylated hydroxytoluene treatment also did not affect sciatic nerve capillary density. We conclude that oxidative stress makes an important contribution to the aetiology of early experimental diabetic neuropathy. Amelioration of oxidative stress could potentially be a final common mechanism whereby a number of diverse treatments exert a beneficial effect on diabetic nerve function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Butylated Hydroxytoluene / therapeutic use*
  • Capillaries / drug effects
  • Capillaries / physiopathology*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Neuropathies / prevention & control*
  • Fructose / metabolism
  • Hypoxia / physiopathology
  • Inositol / metabolism
  • Male
  • Motor Neurons / drug effects
  • Motor Neurons / physiology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiopathology
  • Muscles / innervation*
  • Neural Conduction / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / blood supply
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / physiopathology*
  • Sorbitol / metabolism


  • Butylated Hydroxytoluene
  • Fructose
  • Inositol
  • Sorbitol