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 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 the autoxidation and neurotoxicity 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 the reaction. The presence of AA induced a reduction in the consumption of O2 during the autoxidation of 6-OHDA and a negligible presence of the p-quinone, which demonstrates the efficiency of AA to act as a redox cycling agent. The presence of GSH, CySH, and NAC produced a significant reduction in the autoxidation of 6-OHDA. In vivo, the presence of sulfhydryl antioxidants protected against neuronal degeneration in the striatum, which was particularly 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 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.
Soto-Otero
R
R
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Santiago de Compostela, Spain. bnsoto@uscmail.usc.es
Méndez-Alvarez
E
E
Hermida-Ameijeiras
A
A
Muñoz-Patiño
A M
AM
Labandeira-Garcia
J L
JL
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D016627:Oxidopamine / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010101:Oxygen Consumption / Q000502:physiology; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*
D000975:Antioxidants; D016166:Free Radical Scavengers; D013565:Sympatholytics; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D005978:Glutathione; D003545:Cysteine; D001205:Ascorbic Acid; D000111:Acetylcysteine