Superoxide dismutase partially prevents sympathetic denervation by 6-hydroxydopamine

Summary The effects of superoxide dismutase (S.O.D.) in two models of chemical denervation induced by 6-hydroxydopamine (6-OHDA) were studied.To evaluate the effects of S.O.D. on in vitro 6-OHDA-induced denervation, fragments of the lateral saphenous veins of mongrel dogs were pre-incubated in oxygenated Krebs-Henseleit solution with or without S.O.D. and then incubated under control conditions, with 6-OHDA or with 6-OHDA + S.O.D. Following the incubation period the fragments were repeatedly washed with Krebs solution and then used for determination of noradrenaline and for morphological study. 6-OHDA produced a profound depletion of noradrenaline. This depletion was significantly reduced although not prevented by S.O.D. The protective effect of S.O.D. was concentration-dependent. The ultrastructural study confirmed the 6-OHDA-induced sympathetic nerve degeneration as well as the protective effect afforded by S.O.D.In order to evaluate the effects of S.O.D. on in vivo 6-OHDA-induced denervation, male Wistar rats were anaesthetized and the tail vein cannulated. Saline or S.O.D. were intravenously delivered. 6-OHDA was injected five minutes after the beginning of infusions. Fragments of the left ventricle and vasa deferentia were used for determination of noradrenaline and for morphological study. 6-OHDA produced a significant depletion of noradrenaline in the left ventricle and vas deferens (to 8% and 18% of control values respectively). This depletion was reduced, though not prevented by S.O.D. Morphological data confirmed the neurotoxic effect of 6-OHDA and a protective role for S.O.D.In the concentration shown to afford protection against in vitro 6-OHDA-induced denervation, S.O.D. neither chemically inactivated 6-OHDA, nor did it exert any blocking effect on the neuronal uptake of ³H-noradrenaline. Thus, the protection afforded by S.O.D. against chemical denervation by 6-OHDA appears to be due to the free radical scavenging effect of S.O.D. Send offprint requests to A. Albino-Teixeira at the above address