Oxidative stress participates in the breakdown of neuronal phenotype in experimental diabetic neuropathy

Diabetologia. 2001 Apr;44(4):424-8. doi: 10.1007/s001250051638.


Aims/hypothesis: This study compared the effects of streptozotocin-induced diabetes in rats with those of two pro-oxidant interventions; a diet deficient in vitamin E and treatment with primaquine.

Methods: Measurements were made by the classic motor and sensory conduction velocity deficits and by indicators of the breakdown of small fibre phenotype i.e., sciatic nerve content of nerve growth factor and the neuropeptides, substance P and neuropeptide Y.

Results: As with diabetes, the pro-oxidant interventions decreased conduction velocities (though the effect of vitamin E deficiency was not significant), the sciatic nerve content of nerve growth factor and the neuropeptides (all percentages refer to the mean value for the appropriate control groups). In diabetes, nerve growth factor was depleted to 50% in the control rats (p < 0.05); oxidative stress depleted nerve growth factor to 64% (primaquine; p < 0.05) and 81% (vitamin E deficient; not significant) of controls. Substance P was depleted to 51% in the control rats (p < 0.01) with depletions to 74% and 72% (both p < 0.01) by oxidative stress; equivalent depletions for neuropeptide Y were 38% controls in diabetes (p < 0.001) and 67% (primaquine; p < 0.001) and 74% (vitamin E deficient; p < 0.05) for oxidative stress.

Conclusion/interpretation: The relative magnitudes of these changes suggest an effect in diabetes of oxidative stress, coupled with some other cellular event(s). This is supported by the effects of a diester of gamma-linolenic acid and alpha-lipoic acid, which completely prevented the effects on the pro-oxidant interventions on conduction velocity, nerve growth factor and neuropeptide contents, but was only partially preventative in diabetes.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Neuropathies / pathology
  • Diabetic Neuropathies / physiopathology*
  • Male
  • Nerve Growth Factor / metabolism
  • Neural Conduction
  • Neurons / physiology*
  • Neuropeptide Y / metabolism
  • Oxidative Stress*
  • Phenotype*
  • Primaquine / pharmacology
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / metabolism
  • Substance P / metabolism
  • Thioctic Acid / pharmacology
  • Vitamin E / analysis
  • gamma-Linolenic Acid / pharmacology


  • Neuropeptide Y
  • Vitamin E
  • Substance P
  • Thioctic Acid
  • gamma-Linolenic Acid
  • Nerve Growth Factor
  • Primaquine