Interaction between oxidative stress and gamma-linolenic acid in impaired neurovascular function of diabetic rats.
Nerve conduction and perfusion deficits in diabetic rats depend on increased oxidative stress and impaired n-6 essential fatty acid metabolism, which are corrected by free radical scavenger and gamma-linolenic acid (GLA)-rich oil treatments, respectively. We investigated the interaction between these mechanisms on conduction velocity and endoneurial blood flow by use of low-dose antioxidant (BM15.0639) and GLA treatments, alone and in combination. After 8 wk of streptozotocin-induced diabetes, sciatic motor conduction velocity was 20.9% reduced. Treatment with GLA or BM15.0639 for the final 2 wk corrected this deficit by 18.5 and 20.0%, respectively; however, joint treatment caused 71.5% improvement, corresponding to a 7.5-fold amplification of individual drug effects. A 48.3% deficit in sciatic nutritive endoneurial blood flow was corrected by 34.8 and 24.8% with GLA and BM15.0639 treatments, respectively. With joint treatment, the flow improvement of 72.5% was greater than expected from individual drug effects, indicating a facilitatory interaction. Thus the synergistic effect of combined antioxidant and n-6 essential fatty acid treatment could potentially provide increased therapeutic power against diabetic neuropathy.
Cameron
N E
NE
Department of Biomedical Sciences, University of Aberdeen, Scotland, United Kingdom.
Cotter
M A
MA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D018384:Oxidative Stress; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017965:gamma-Linolenic Acid / Q000378:metabolism* / Q000494:pharmacology
D000975:Antioxidants; D010636:Phenols; C088480:BM 15.0639; D017965:gamma-Linolenic Acid