EFFECTS OF NATURAL FREE-RADICAL SCAVENGERS ON PERIPHERAL-NERVE AND NEUROVASCULAR FUNCTION IN DIABETIC RATS

Increased generation of reactive oxygen species, coupled with impaired endogenous scavenging mechanisms, plays a prominent role in the aetio logy of neurovascular abnormalities in experimental diabetes mellitus. We examined the efficacy of the natural anti-oxidants vitamins C, E a nd beta-carotene in preventing nerve conduction and nutritive blood fl ow deficits in streptozotocin-diabetic rats. One month of diabetes cau sed a 19.1% reduction in sciatic motor conduction velocity (p < 0.001) . This was approximately prevented 80-90% by high-dose (1000 mg . kg(- 1). day(-1)) vitamin E and beta-carotene treatments (p < 0.001). Vitam in C had lesser effects; the maximum protection found for motor conduc tion velocity was 36% using a dose of 150 mg . kg(-1). day(-1) (p < 0. 001). High dose (500 mg . kg(-)1 . day(-1)) vitamin C had a lesser eff ect on conduction than intermediate doses. Joint vitamin C and lower d ose (500 mg . kg(-1). day(-1)) vitamin E treatment had a predominantly additive preventive effect against nerve dysfunction. Resistance to h ypoxic conduction failure for sciatic nerve in vitro was markedly incr eased by diabetes and this remained relatively unaffected by treatment . Sciatic nutritive endoneurial blood flow, measured using microelectr ode polarography and hydrogen clearance, was reduced 46.1% by 1 month of diabetes (p < 0.001). This was prevented to the extent of 87 %, 36 % and 98 % by vitamins E, C and beta-carotene, respectively (p < 0.01) . These data emphasize the role of oxidative stress in the development of early neurovascular changes in experimental diabetes and show that naturally available scavengers have a neuroprotective action.