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 Al 3+, 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 Al 3+, while the effect of sulfhydryl reductants was limited to only the first few minutes of the reaction. However, both Al 3+ and Zn 2+ 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 Al 3+ induced a significant reduction in lipid peroxidation. After intrastriatal injections of 6-OHDA in rats, tyrosine hydroxylase immunohistochemistry revealed that Al 3+ 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 Al 3+ accumulation. The previously reported antioxidant properties of Zn 2+ appear to be related to the induction of Zn 2+-containing proteins and not to the metal per se.