Salicylate inhibits LDL oxidation initiated by superoxide nitric oxide radicals

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 EDL from oxidation by O2 .-/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 mag indicate that salicylate could act as an efficacious inhibitor of O-2(.-)/NO. Initiated atherogenic LDL modification, thus further supporting the rationale of aspirin meditation regarding cardiovascular diseases. (C) 1999 Federation of European Biochemical Societies.