Superoxide dismutase partially prevents sympathetic denervation by 6-hydroxydopamine.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Albino-Teixeira
A
A
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Azevedo
I
I
Martel
F
F
Osswald
W
W
D000818:Animals; D004285:Dogs; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012501:Saphenous Vein / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013562:Sympathectomy
D016627:Oxidopamine; D013482:Superoxide Dismutase; D009638:Norepinephrine