The salicylate metabolite gentisic acid, but not the parent drug, inhibits glucose autoxidation-mediated atherogenic modification of low density lipoprotein.
Oxidation of low density lipoprotein (LDL) by glucose-derived radicals may play a role in the aetiology of atherosclerosis in diabetes. Salicylate was shown to scavenge certain radicals. In the present study, aspirin, salicylate and its metabolites 2,5- and 2, 3-dihydroxybenzoic acid (DHBA) were tested for their ability to impair LDL oxidation by glucose. Only the DHBA derivatives, when present during LDL modification, inhibited LDL oxidation and the increase in endothelial tissue factor synthesis induced by glucose oxidised LDL. The LDL glycation reaction was not affected by DHBA. The antioxidative action of DHBA may be attributed to free radical scavenging and/or chelation of transition metal ions catalysing glucose autoxidation.
Exner
M
M
Department of Laboratory Medicine, University of Vienna, Vienna, Austria.
Hermann
M
M
Hofbauer
R
R
Kapiotis
S
S
Speiser
W
W
Held
I
I
Seelos
C
C
Gmeiner
B M
BM
D001161:Arteriosclerosis / Q000517:prevention & control*; D001241:Aspirin / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005841:Gentisates; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D062385:Hydroxybenzoates / Q000378:metabolism / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000378:metabolism / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020156:Salicylic Acid / Q000378:metabolism / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis
D005841:Gentisates; D062385:Hydroxybenzoates; D007502:Iron Chelating Agents; D008077:Lipoproteins, LDL; D011355:Prodrugs; D017382:Reactive Oxygen Species; C009135:2,3-dihydroxybenzoic acid; D013925:Thromboplastin; D005947:Glucose; D020156:Salicylic Acid; D001241:Aspirin; C010925:2,5-dihydroxybenzoic acid