Antioxidant action of neuromelanin: the mechanism of inhibitory effect on lipid peroxidation.

Iron and lipid peroxidation are believed to be involved in the degeneration of pigmented neurons in Parkinson's disease. Melanin-iron interaction is thought to play a role in iron accumulation and reactivity. The purpose of this study was to examine antioxidant properties of isolated natural and synthetic neuromelanin. Effect of neuromelanin from substantia nigra and its synthetic model, dopamine melanin, on lipid peroxidation, induced by ferrous ions and free-radical initiators, has been studied in methyl linoleate aqueous dispersions. 2,2'-Azobis(amidinopropane)dihydrochloride and 2,2'-azobis(2,4-dimethyl-valeronitrile) were used as water-soluble and lipid-soluble radical initiator, respectively. Rate of oxidation was followed quantitatively by measuring oxygen uptake and accumulation of lipid hydroperoxides. Melanin had a distinct protective effect on lipid peroxidation induced by ferrous ions or water-soluble free-radical initiator but was relatively inefficient when peroxidation was initiated with lipid-soluble compound. It also inhibited iron-catalyzed decomposition of methyl linoleate hydroperoxides in the presence of ascorbate. Extent of the inhibition depended on the ratio of melanin to iron. Taken together, these results provide strong support for the idea that neuromelanin of pigmented neurons can act as a natural antioxidant by sequestering redox-active metal ions.