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 Al³⁺ was dependent on melanin (10-100 μg/ml) and Al³⁺ (2.5-250 μM) 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 Q₂/·^-, Ga³⁺ and Be²⁺ which can increase NADH oxidation in the presence of Q₂/·^-, 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.