Comparative effects of melatonin, L-deprenyl, Trolox and ascorbate in the suppression of hydroxyl radical formation during dopamine autoxidation in vitro

Degeneration of nigrostriatal dopaminergic neurons is the major pathogenic substrate of Parkinson's disease (PD). Inhibitors of monoamine oxidase B (M AO-B) have been used in the treatment of PD and at least one of them, i.e., deprenyl, also displays antioxidant activity. Dopamine (DA) autoxidation p roduces reactive oxygen species implicated in the loss of dopaminergic neur ons in the nigrostriatal pathway. In this study we compared the effects of melatonin with those of deprenyl and vitamins E and C in preventing the hyd roxyl radical (. OH) generation during DA oxidation. The rate of production of 2,3-dihydroxybenzoate (2,3-DHBA) in the presence of salicylate, an . OH scavenger, was used to detect the in vitro generation of . OH during iron- catalyzed oxidation of DA. The results showed a dose-dependent effect of me latonin, deprenyl and vitamin E in counteracting DA autoxidation, whereas v itamin C had no effect. Comparative analyses between the effect of these an tioxidants showed that the protective effect of melatonin against DA autoxi dation was significantly higher than that of the other compounds tested. Al so, when melatonin plus deprenyl were added to the incubation medium, a pot entiation of the antioxidant effect was found. These findings suggest that antioxidants may be useful in brain protection against toxicity of reactive oxygen species produced during DA oxidation, and melatonin, alone or in co mbination with deprenyl, may be an important component of the brain's antio xidant defenses to protect it from dopaminergic neurodegeneration.