Summary
Increased oxygen free radical activity, coupled with reduced protection against oxidative stress, could play a role in the aetiology of neurovascu-lar abnormalities in experimental diabetes mellitus. To test this hypothesis, non-diabetic and streptozotocin-diabetic rats were treated with the anti-oxidant probu-col 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.
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Abbreviations
- GSH:
-
reduced glutathione
- OFR:
-
oxygen free radical
- NCV:
-
nerve conduction velocity
- ACE:
-
angiotensin converting enzyme
- EMG:
-
electromyogram
- NO:
-
nitric oxide
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Cameron, N.E., Cotter, M.A., Archibald, V. et al. Anti-oxidant and pro-oxidant effects on nerve conduction velocity, endoneurial blood flow and oxygen tension in non-diabetic and streptozotocin-diabetic rats. Diabetologia 37, 449–459 (1994). https://doi.org/10.1007/s001250050131
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DOI: https://doi.org/10.1007/s001250050131