Autoxidation and neurotoxicity of 6-hydroxydopamine in the presence of some antioxidants: Potential implication in relation to the pathogenesis of Parkinson's disease

6-Hydroxydopamine (6-OHDA) is a dopaminergic neurotoxin putatively involved in the pathogenesis of Parkinson's disease (PD). Its neurotoxicity has bee n related to the production of reactive oxygen species. In this study we ex amine the effects of the antioxidants ascorbic acid (AA), glutathione (GSH) , cysteine (CySH), and N-acetyl-CySH (NAC) on the autoxidation and neurotox icity of 6-OHDA. In vitro, the autoxidation of 6-OHDA proceeds rapidly with the formation of H2O2 and with the participation of the H2O2 produced in t he reaction. The presence of AA induced a reduction in the consumption of O -2 during the autoxidation of 6-OHDA and a negligible presence of the p-qui none, which demonstrates the efficiency of AA to act as a redox cycling age nt. The presence of GSH, CySH, and NAC produced a significant reduction in the autoxidation of 6-OHDA. In vivo, the presence of sulfhydryl antioxidant s protected against neuronal degeneration in the striatum, which was partic ularly remarkable in the case of CySH and was attributed to its capacity to remove the H2O2 produced in the autoxidation of 6-OHDA. These results corr oborate the involvement of oxidative stress as the major mechanism in the n eurotoxicity of 6-OHDA and the putative role of CySH as a scavenger in rela tion to PD.