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 peroxida tion in liposomes and rat caudate-putamen homogenates. Al3+ stimulated mela nin-initiated lipid peroxidation as measured by the production of.-thiobarb ituric acid-reactive substances (TBARS) and conjugated dienes. The effect o f Al3+ was dependent on melanin (10-100 mu g/ml) and Al3+ (2.5-250 mu M) co ncentrations and no synergism between Fe2+ and Al3+ was observed. The proox idant effect of Al3+ was partially inhibited by superoxide dismutase indica ting the involvement of O-2(.-). Ga3+ and Be2+ which can increase NADH oxid ation in the presence of O-2(-), also were shown to stimulate melanin-initi ated TEARS production. Based on the effect of Al3+ and other non redox meta ls, we suggest that Al3+ does not act through either the induction of melan in free radicals, or the induction of changes in membrane physical properti es. Results show that Al3+ enhances melanin-initiated lipid peroxidation in part through an interaction with O-2(-) generated from the autoxidation of melanin. We speculate that Al3+ contributes to neuromelanin-mediated oxida tive damage in dopaminergic neurons and subsequent neuronal degeneration an d death in Parkinson's disease.