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

• Published in: Archives of biochemistry and biophysics Vol. 423; no. 2; pp. 302 - 308
• Main Authors: Sanguinetti, Silvia M, Batthyány, Carlos, Trostchansky, Andrés, Botti, Horacio, López, Graciela I, Wikinski, Regina L.W, Rubbo, Homero, Schreier, Laura E
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-03-2004
• Subjects: Alkenes - chemistry; Alkenes - metabolism; alpha-Tocopherol - chemistry; alpha-Tocopherol - metabolism; Antioxidant; Antioxidants - physiology; Copper; Copper - chemistry; Free radical; Humans; LDL oxidation; Lipoproteins, LDL - chemistry; Lipoproteins, LDL - metabolism; Nitric oxide; Nitric Oxide - physiology; Oxidants - antagonists & inhibitors; Oxidants - toxicity; Oxidation-Reduction; Spectrometry, Fluorescence; Uric acid; Uric Acid - antagonists & inhibitors; Uric Acid - toxicity; Uric acid; Copper; Antioxidant; Nitric oxide; Free radical; LDL oxidation
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2003.12.034

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.