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)-N-.) during copper-mediated low-density lipoprotein (LDL) oxidation were evaluated. In the absence of (NO)-N-., a dual pro- and antioxidant action of uric acid was evident: low concentrations of uric acid enhanced lipid oxidation and alpha-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)-N-., the antioxidant action of (NO)-N-. was slightly counterbalanced by uric acid. Enhancement of alpha-tocopherol consumption by uric acid was inhibited in the presence of (NO)-N-. while additive antioxidant effects between (NO)-N-. and uric acid were observed in conditions where uric acid spared alpha-tocopherol. Altogether, these results suggest that in the artery wall, the (NO)-N-./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. (C) 2004 Elsevier Inc. All rights reserved.