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 superoxide on iron oxidation and reduction revealed that superoxide is a better oxidant of ADP:Fe(II) than a reductant of ADP:Fe(III). 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(II) oxidation or Fe(III) reduction necessary for lipid peroxidation. The relevance of the reactions of O2-. and H2O2 on physiological chelates of iron are discussed.