Interaction of Melanin with Metal Ions Modulates Their Cytotoxic Potential

Melanin is one the most common biological pigments. In humans, specialized cells called melanocytes synthesize the pigment from tyrosine and 3,4-dihydroxyphenylalanine via enzyme-catalyzed reactions and spontaneous processes. The formed melanin granule consists of nanoaggregates of oligomers containing different monomers. Although the main biological function of melanin is protection against damage from solar radiation, melanin may also be involved in protection against oxidative stress. In the latter function, sequestration of redox-active metal ions and scavenging of reactive oxygen species are of importance. The paper reviews basic physicochemical properties of melanin responsible for binding of metal ions and discusses specific conditions that may induce cytotoxicity of metal ions such as iron and copper by facilitating their redox activation and release from melanin. While the value of EPR spectroscopy and other EPR-related techniques for the study of melanin is emphasized, the concomitant use of other physicochemical methods is the most efficient approach.