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Salicylate inhibits LDL oxidation initiated by superoxide/nitric oxide radicals
Author(s) -
Hermann Marcela,
Kapiotis Stylianos,
Hofbauer Roland,
Exner Markus,
Seelos Christian,
Held Irmtraud,
Gmeiner Bernhard
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00043-5
Subject(s) - chemistry , peroxynitrite , superoxide , nitric oxide , radical , nitration , oxidative phosphorylation , biochemistry , pharmacology , tbars , aspirin , antioxidant , lipid peroxidation , organic chemistry , enzyme , medicine
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.