Nitric oxide inhibits prooxidant actions of uric acid during copper-mediated LDL oxidation

Interactions between uric acid and physiologically relevant fluxes of nitric oxide (NO) during copper-mediated low-density lipoprotein (LDL) oxidation were evaluated. In the absence of NO, a dual pro- and antioxidant action of uric acid was evident: low concentrations of uric acid enhanced lipid oxidation and α-tocopherol consumption, while its protective role was observed at higher concentrations. The prooxidant effects of uric acid were mostly related to its copper-reducing ability to form Cu+, an initiator of lipid oxidation processes. While the prooxidant action of uric acid was completely inhibited by NO, the antioxidant action of NO was slightly counterbalanced by uric acid. Enhancement of α-tocopherol consumption by uric acid was inhibited in the presence of NO while additive antioxidant effects between NO and uric acid were observed in conditions where uric acid spared α-tocopherol. Altogether, these results suggest that in the artery wall, the NO/uric acid pair may exert antioxidant actions on LDL, even if increased amounts of redox active copper were available at conditions favoring prooxidant activities of uric acid.