Xanthine Oxidase- and Iron-Dependent Lipid Peroxidation

Xanthine oxidase and iron-dependent lipid peroxidation has been studied extensively in many model systems, yet several details of this process remain unclear. Because redox reactions of iron are important parameters of iron-catalyzed lipid peroxidation, we have examined the roles of superoxide and hydrogen peroxide, produced by xanthine oxidase, to oxidize and reduce iron and thereby affect iron-catalyzed lipid peroxidation. Thus, we compared lipid peroxidation catalyzed by xanthine oxidase and ADP:Fe(III) to that catalyzed by xanthine oxidase and ADP:Fe(II). An examination of the action of super-oxide on iron oxidation and reduction revealed that superoxide is a better oxidant of ADP:Fe(II) than a reductant of ADP:Fe(IIl). A superoxide generating system (composed of xanthine oxidase and catalase) and ADP:Fe(II) also resulted in a greater amount of lipid peroxidation than superoxide and ADP:Fe(III). Hydrogen peroxide, as expected, only served as an Fe(II) oxidant. A comparison of the oxidant activities of either superoxide or hydrogen peroxide on ADP:Fe(II) and the corresponding effects on lipid peroxidation revealed that both oxidants were roughly equivalent. We conclude that superoxide and hydrogen peroxide, produced from xanthine oxidase, support iron-catalyzed lipid peroxidation through their participation in redox reactions of iron, that is, they facilitate Fe(TI) oxidation or Fe(III) reduction necessary for lipid peroxidation. The relevance of the reactions of O⨪2 and H2O2 on physiological chelates of iron are discussed.