Aluminum enhances melanin-induced lipid peroxidation.
The present study was conducted to characterize the possible interaction of Al3+ and Fe2+ with synthetic melanin in the potentiation of lipid peroxidation in liposomes and rat caudate-putamen homogenates. Al3+ stimulated melanin-initiated lipid peroxidation as measured by the production of 2-thiobarbituric acid-reactive substances (TBARS) and conjugated dienes. The effect of A13+ was dependent on melanin (10-100 microg/ml) and A13+ (2.5-250 microM) concentrations and no synergism between Fe2+ and Al3+ was observed. The prooxidant effect of Al3+ was partially inhibited by superoxide dismutase indicating the involvement of O2*- . Ga3+ and Be2+ which can increase NADH oxidation in the presence of O2*-, also were shown to stimulate melanin-initiated TBARS production. Based on the effect of Al3+ and other non redox metals, we suggest that Al3+ does not act through either the induction of melanin free radicals, or the induction of changes in membrane physical properties. Results show that Al3+ enhances melanin-initiated lipid peroxidation in part through an interaction with O2*- generated from the autoxidation of melanin. We speculate that Al3+ contributes to neuromelanin-mediated oxidative damage in dopaminergic neurons and subsequent neuronal degeneration and death in Parkinson's disease.
Meglio
L
L
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Oteiza
P I
PI
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008543:Melanins / Q000494:pharmacology*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D012395:Rose Bengal / Q000737:chemistry; D013482:Superoxide Dismutase / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D008543:Melanins; D017392:Thiobarbituric Acid Reactive Substances; D009243:NAD; D012395:Rose Bengal; D000535:Aluminum; D013482:Superoxide Dismutase