Peroxynitrite flux-mediated LDL oxidation is inhibited by manganese porphyrins in the presence of uric acid

• Published in: Free radical biology & medicine Vol. 35; no. 10; pp. 1293 - 1300
• Main Authors: Trostchansky, Andrés, Ferrer-Sueta, Gerardo, Batthyány, Carlos, Botti, Horacio, Batinić-Haberle, Ines, Radi, Rafael, Rubbo, Homero
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.11.2003
• Subjects: alpha-Tocopherol - metabolism; Atherogenesis; Free radicals; gamma-Tocopherol - metabolism; Humans; Hydrogen Peroxide - metabolism; LDL; Lipid oxidation; Lipoproteins, LDL - chemistry; Manganese - metabolism; Metalloporphyrins - chemistry; Metalloporphyrins - metabolism; Metalloporphyrins - pharmacology; Mn(III)porphyrins; Nitric oxide; Nitrogen Dioxide - metabolism; Oxidation-Reduction; Peroxynitrite; Peroxynitrous Acid - pharmacology; Uric Acid - metabolism; Atherogenesis; Peroxynitrite; Free radicals; Mn(III)porphyrins; LDL; Nitric oxide; Lipid oxidation
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2003.07.004

We have studied the role of three Mn(III)porphyrins differing in charge, alkyl substituent length and reactivity, on LDL exposed to low fluxes of peroxynitrite (PN) in the presence of uric acid. Mn(III)porphyrins (5 μM, MnTE-2-PyP 5+, MnTnOct-2-PyP 5+, and MnTCPP 3−) plus uric acid (300 μM) inhibited cholesteryl ester hydroperoxide formation, changes in REM as well as spared α- and γ-tocopherol. MnTnOct-2-PyP 5+, the more lipophilic compound, was the most effective in protecting LDL lipids, while MnTCPP 3− exerted the lesser protection. Mn(III)porphyrins react fast with PN (∼10 5−10 7 M −1 s −1) to yield a O=Mn(IV) complex. The stoichiometry of uric acid consumption was ∼1.7 moles per mol of PN, in agreement with reactions with both the O=Mn(IV) complex and nitrogen dioxide. A shift from an anti- to a pro-oxidant action of the Mn(III)porphyrin was observed after uric acid was significantly consumed, supporting competition reactions between LDL targets and uric acid for the O=Mn(IV) complex. Overall, the data is consistent with the catalytic reduction of PN in a cycle that involves a one electron oxidation of Mn(III) to Mn(IV) by PN followed by the reduction back to Mn(III) by uric acid. These antioxidant effects should predominate under in vivo conditions having plasma uric acid concentration range between 150 and 500 μM.