Reversal of peripheral nerve conduction and perfusion deficits by the free radical scavenger, BM15.0639, in diabetic rats.
We examined the ability of the oxygen free radical scavenger, BM 15.0639 (400 mg kg-1 day-1), to correct existing sciatic motor nerve conduction velocity and endoneurial blood flow deficits in streptozotocin-diabetic rats. Rats were treated for 1 month following 1 month of untreated diabetes. Effects of treatment in non-diabetic rats were also examined. A further experiment determined the dose-response relationship for correction of conduction velocity abnormalities by BM15.0639. Diabetes caused 20.9% and 22.7% deficits in motor conduction velocity after 1 and 2 months respectively (both P < 0.001). Rats treated with BM15.0639 after the first month of untreated diabetes had conduction velocity values that were not significantly different from those for non-diabetic controls, but were significantly elevated compared to 1 or 2 months untreated diabetes (both P < 0.001). The ED50 for correction of nerve conduction velocity was approximately 36 mg kg-1 day-1. Sciatic nutritive endoneurial blood flow was 46.5% and 50.5% decreased by 1 and 2 months diabetes respectively (both P < 0.001). This was more than corrected by BM15.0639 treatment of diabetic rats, flow being approximately 33% greater than normal (P < 0.05). In contrast, 1 month BM15.0639 treatment had no effect on blood flow or conduction velocity in non-diabetic rats. Co-treatment of BM15.0639-treated diabetic rats with the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (10 mg kg-1 day-1) largely abolished the anti-oxidant effect on conduction velocity and blood flow. Thus, the data highlight the importance of oxygen free radical activity for the neurovascular deficits in experimental diabetes which are at least in part caused by impaired NO production or release.
Cameron
N E
NE
Department of Biomedical Sciences, University of Aberdeen, UK.
Cotter
M A
MA
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007928:Lethal Dose 50; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000633:toxicity; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects*; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity
D000975:Antioxidants; D016166:Free Radical Scavengers; D010636:Phenols; C088480:BM 15.0639; D019335:Nitroarginine; D013311:Streptozocin; D019001:Nitric Oxide Synthase