Inhibitory effect of zinc(II) on free radical lipid peroxidation in erythrocyte membranes.

New evidence in support of zinc's role as a membrane antioxidant is presented. Human erythrocyte membranes in buffered saline underwent catalase- and superoxide dismutase-inhibitable lipid peroxidation when incubated with xanthine, xanthine oxidase, and Fe(III). Free radical mediated peroxidation was measured in terms of thiobarbituric acid reactivity and iodometric determination of lipid hydroperoxides. Whereas Ca(II) had relatively little effect on lipid peroxidation, Zn(II) strongly inhibited the reaction and suppressed peroxidation-dependent lysis of resealed membranes. Inhibition of lipid peroxidation was essentially complete in the presence of 0.1 mM Zn(II), a concentration equivalent to that of added Fe(III). By contrast, Zn(II) had no effect on rose bengal-photosensitized lipid peroxidation, a predominantly nonradical, singlet oxygen-driven process. Zinc(II) also interfered with xanthine/xanthine oxidase/iron-induced peroxidation of Triton X-100-dispersed membranes, but had no effect if EDTA was present. Trivial reasons for inhibition, for example, inactivation of xanthine oxidase or complex formation with O2-, were ruled out by showing that the rate of reduction of cytochrome c by xanthine/xanthine oxidase is not affected by Zn(II). We speculate that Zn(II) acts by interfering with the redox cycling of iron, possibly by competing with the latter for membrane binding sites.