Antioxidant action of xanthurenic acid : Inhibition of lipid peroxidation and protection for NADP-isocitrate dehydrogenase

Abstract

Vitamin B6 deficiency increases the lipid peroxidation and the synthesis of xanthurenic acid from tryptophan. Antioxidant properties of xanthurenic acid were examined in relation to the coordination of transition metals. Xanthurenic acid inhibited the formation of thiobarbituric acid-reactive substances as a marker of iron-mediated lipid peroxidation, and copper-dependent oxidation of low density lipoprotein. NADP-isocitrate dehydrogenase and malic enzyme, principal NADPH-generating enzymes for antioxidant defense system, was inactivated by reduced iron, and xanthurenic acid protected the enzyme from this inactivation. Xanthurenic acid may participate in the enhanced regeneration of reduced glutathione by stimulating NADPH supply. Xanthurenic acid further enhanced the autooxidation of Fe²⁺ ion. Other tryptophan metabolites such as kynurenic acid and quinaldic acid did not inhibit the lipid peroxidation and the inactivation of NADP-isocitrate dehydrogenase, and showed little or no effect on the Fe²⁺ autooxidation. Antioxidant properties of xanthurenic acid are related to the metal-chelating activity and probably to the enhanced oxidation of reduced transition metals as prooxidant.