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Autoxidation and Neurotoxicity of 6‐Hydroxydopamine in the Presence of Some Antioxidants
Author(s) -
SotoOtero Ramón,
MéndezÁlvarez Estefanía,
HermidaAmeijeiras Álvaro,
MuñozPatiño Ana María,
LabandeiraGarcia José Luis
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741605.x
Subject(s) - autoxidation , chemistry , hydroxydopamine , neurotoxicity , oxidative stress , ascorbic acid , glutathione , neurotoxin , reactive oxygen species , biochemistry , pharmacology , dopaminergic , toxicity , dopamine , organic chemistry , biology , endocrinology , food science , enzyme
6‐Hydroxydopamine (6‐OHDA) is a dopaminergic neurotoxinputatively involved in the pathogenesis of Parkinson's disease (PD). Itsneurotoxicity has been related to the production of reactive oxygen species.In this study we examine the effects of the antioxidants ascorbic acid (AA),glutathione (GSH), cysteine (CySH), and N ‐acetyl‐CySH (NAC) on theautoxidation and neurotoxicity of 6‐OHDA. In vitro, the autoxidation of 6‐OHDAproceeds rapidly with the formation of H 2 O 2 and with theparticipation of the H 2 O 2 produced in the reaction. Thepresence of AA induced a reduction in the consumption of O 2 duringthe autoxidation of 6‐OHDA and a negligible presence of the p ‐quinone, which demonstrates the efficiency of AA to act as a redoxcycling agent. The presence of GSH, CySH, and NAC produced a significantreduction in the autoxidation of 6‐OHDA. In vivo, the presence of sulfhydrylantioxidants protected against neuronal degeneration in the striatum, whichwas particularly remarkable in the case of CySH and was attributed to itscapacity to remove the H 2 O 2 produced in the autoxidation of 6‐OHDA. These results corroborate the involvement of oxidative stress as the major mechanism in the neurotoxicity of 6‐OHDA and the putative role of CySH as a scavenger in relation to PD.