Antioxidant properties of ticlopidine on human low density lipoprotein oxidation.
We found that ticlopidine, at therapeutically relevant concentrations (2.5-10 microM), but not aspirin nor salicylate, significantly counteracted copper-driven human LDL oxidation. Ticlopidine, at 5 and 10 microM, was also antioxidant on peroxyl radical-induced LDL oxidation; yet it was ineffectual on thiol and ascorbate oxidation mediated by peroxyl radicals themselves, suggesting that drug antioxidant capacity is somehow related to the lipoprotein nature of the oxidizable substrate, but not to radical scavenging. The drug could not indeed react with the stable free radical 1,1-diphenyl-2-pycrylhydrazyl, nor had apparent metal complexing-inactivating activity. Thus, ticlopidine has antioxidant effects on LDL oxidation, which, together with its anti-platelet activity, could confer peculiar antiatherogenic properties to the drug in vivo.
Lapenna
D
D
Dipartimento di Medicina e Scienze dell'Invecchiamento, Università degli Studi G. d'Annunzio, Facoltà di Medicina e Chirurgia, Chieti, Italy.
de Gioia
S
S
Ciofani
G
G
Bruno
C
C
Porreca
E
E
Pierdomenico
S D
SD
Cuccurullo
F
F
D000578:Amidines / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects* / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010545:Peroxides / Q000494:pharmacology; D013988:Ticlopidine / Q000494:pharmacology*
D000578:Amidines; D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D008077:Lipoproteins, LDL; D016877:Oxidants; D010545:Peroxides; C099252:oxidized low density lipoprotein; C049375:perhydroxyl radical; C046728:2,2'-azobis(2-amidinopropane); D013988:Ticlopidine; D001205:Ascorbic Acid; D001241:Aspirin