The antioxidant properties of zinc: Interactions with iron and antioxidants

Potential mechanisms underlying zinc's capacity to protect membranes from l ipid oxidation were examined in liposomes. Using lipid oxidation initiators with different chemical and physical properties (transition metals, lipid- or water-soluble azo compounds, ultraviolet radiation c (UVc), superoxide radical anion (O-2(.-)), and peroxynitrite (ONOO-) we observed that zinc on ly prevented copper (Cu2+)- and iron (Fe2+)-initiated lipid oxidation. In t he presence of Fe2+, the antioxidant action of zinc depended directly on th e negative charge density of the membrane bilayer. An inverse correlation ( r(2): 0.96) was observed between the capacity of zinc to prevent iron bindi ng to the membrane and the inhibitory effect of zinc on Fe2+-initiated lipi d oxidation. The interaction of zinc with the bilayer did not affect physic al properties of the membrane, including rigidification and lateral phase s eparation known to increase lipid oxidation rates. The interactions between zinc and the lipid- (alpha -tocopherol) and water- (epicatechin) soluble a ntioxidants were studied. The inhibition of Fe2+-induced lipid oxidation by either alpha -tocopherol or epicatechin was increased by the simultaneous addition of zinc. The combined actions of alpha -tocopherol (0.01 mol%), ep icatechin (0.5 muM) and zinc (5-50 muM) almost completely prevented Fe2+ (2 5 muM)-initiated lipid oxidation. These results show that zinc can protect membranes from iron-initiated lipid oxidation by occupying negatively charg ed sites with potential iron binding capacity. In addition, the synergistic actions of zinc with lipid and water-soluble antioxidants to prevent lipid oxidation, suggests that zinc is a pivotal component of the antioxidant de fense network that protects membranes from oxidation. (C) 2001 Elsevier Sci ence Inc.