Salicylate inhibits LDL oxidation initiated by superoxide/nitric oxide radicals

FEBS Letters

Hermann, Marcela⁴  Seelos, Christian¹  Held, Irmtraud³  Exner, Markus²  Gmeiner, Bernhard³  Hofbauer, Roland²  Kapiotis, Stylianos² 

[1] Institute of Tumorbiology, University of Vienna, Vienna, Austria;Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Vienna, Austria;Institute of Medical Chemistry, University of Vienna, Währingerstr. 10, A-1090 Vienna, Austria;From the Institute of Molecular Genetics, University of Vienna, Vienna, Austria

关键词: LDL oxidation;    Superoxide;    Nitric oxide;    Antioxidant;    Aspirin;    Salicylate;    SIN-1;   

DOI  :  10.1016/S0014-5793(99)00043-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Simultaneously produced superoxide/nitric oxide radicals (O^⋅− ₂/NO^⋅) could form peroxynitrite (OONO⁻) which has been found to cause atherogenic, i.e. oxidative modification of LDL. Aromatic hydroxylation and nitration of the aspirin metabolite salicylate by OONO⁻ has been reported. Therefore we tested if salicylate may be able to protect LDL from oxidation by O^⋅− ₂/NO^⋅ by scavenging the OONO⁻ reactive decomposition products. When LDL was exposed to simultaneously produced O^⋅− ₂/NO^⋅ using the sydnonimine SIN-1, salicylate exerted an inhibitory effect on LDL oxidation as measured by TBARS and lipid hydroperoxide formation and alteration in electrophoretic mobility of LDL. The cytotoxic effect of SIN-1 pre-oxidised LDL to endothelial cells was also diminished when salicylate was present during SIN-1 treatment of LDL. Spectrophotometric analysis revealed that salicylate was converted to dihydroxybenzoic acid (DHBA) derivatives in the presence of SIN-1. 2,3- and 2,5-DHBA were even more effective to protect LDL from oxidation by O^⋅− ₂/NO^⋅. Because O^⋅− ₂/NO^⋅ can occur in vivo, the results may indicate that salicylate could act as an efficacious inhibitor of O^⋅− ₂/NO^⋅ initiated atherogenic LDL modification, thus further supporting the rationale of aspirin medication regarding cardiovascular diseases.

【 授权许可】

Unknown