title: Effects of aluminum and zinc on the oxidative stress caused by 6-hydroxydopamine autoxidation: relevance for the pathogenesis of Parkinson's disease.
abstract: Aluminum and zinc have been related to the pathogenesis of Parkinson's disease (PD), the former for its neurotoxicity and the latter for its apparent antioxidant properties. 6-Hydroxydopamine (6-OHDA) is an important neurotoxin putatively involved in the pathogenesis of PD, its neurotoxicity often being related to oxidative stress. The potential effect of these metals on the oxidative stress induced by 6-OHDA autoxidation and the potential of ascorbic acid (AA), cysteine, and glutathione to modify this effect were investigated. Both metals, particularly Al3+, induced a significant reduction in *OH production by 6-OHDA autoxidation. The combined action of AA and a metal caused a significant and sustained increase in *OH generation, particularly with Al3+, while the effect of sulfhydryl reductants was limited to only the first few minutes of the reaction. However, both Al3+ and Zn2+ provoked a decrease in the lipid peroxidation induced by 6-OHDA autoxidation using mitochondrial preparations from rat brain, assessed by TBARS formation. In the presence of AA, only Al3+ induced a significant reduction in lipid peroxidation. After intrastriatal injections of 6-OHDA in rats, tyrosine hydroxylase immunohistochemistry revealed that Al3+ reduces 6-OHDA-induced dopaminergic lesion in the striatum, which corroborates the involvement of lipid peroxidation in 6-OHDA neurotoxicity and appears to discard the participation of this mechanism on PD by Al3+ accumulation. The previously reported antioxidant properties of Zn2+ appear to be related to the induction of Zn2+-containing proteins and not to the metal per se.
authors.affiliation: Grupo de Neuroquímica, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Santiago de Compostela, San Francisco 1, E-15782, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Méndez-Alvarez
authors.forename: Ramón
authors.initials: R
authors.lastname: Soto-Otero
authors.forename: Alvaro
authors.initials: A
authors.lastname: Hermida-Ameijeiras
authors.forename: Ana María
authors.initials: AM
authors.lastname: López-Real
authors.forename: José Luis
authors.initials: JL
authors.lastname: Labandeira-García
mesh_terms: D018663:Adrenergic Agents; D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002412:Cations; D003545:Cysteine / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000032:analysis / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016627:Oxidopamine; D010101:Oxygen Consumption; D011048:Polarography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013053:Spectrophotometry; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D015032:Zinc / Q000494:pharmacology*
chemical_list: D018663:Adrenergic Agents; D000975:Antioxidants; D002412:Cations; D017392:Thiobarbituric Acid Reactive Substances; D017665:Hydroxyl Radical; D016627:Oxidopamine; D000535:Aluminum; D005978:Glutathione; D015032:Zinc; D003545:Cysteine; D001205:Ascorbic Acid