title: Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma.
abstract: Gentisic acid, an aspirin metabolite, has an antioxidant effect, although its detailed mechanism remains elusive. The present study was designed to determine whether it inhibits low-density lipoprotein (LDL) oxidation and the formation of lipid hydroperoxides in human plasma. The susceptibility of LDL oxidative modification was investigated by a method using 2,2'-azobis or Cu2+. To study the effect of gentisic acid on free radical-induced damage to plasma lipids, cholesterol ester hydroperoxides generated by incubating human fresh plasma with Cu2+ and gentisic acid was analyzed. Gentisic acid inhibited LDL oxidation in a concentration-dependent manner. It significantly inhibited the formation of cholesterol ester hydroperoxides in plasma, and was consumed after the depletion of ascorbic acid and reduced form of coenzyme Q-10 (CoQH2-10), whereas concentrations of other antioxidants remained unchanged. Gentisic acid had a potent free radical scavenging activity with a minimal chelating effect. The potent antioxidant property of gentisic acid may partly account for the anti-atherogenic effects of aspirin.
authors.affiliation: Department of Internal Medicine, Kudanzaka Hospital, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ashidate
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Kawamura
authors.forename: Daigo
authors.initials: D
authors.lastname: Mimura
authors.forename: Hisako
authors.initials: H
authors.lastname: Tohda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyazaki
authors.forename: Tamio
authors.initials: T
authors.lastname: Teramoto
authors.forename: Yorihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hirata
mesh_terms: D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001241:Aspirin / Q000378:metabolism*; D001391:Azo Compounds / Q000494:pharmacology; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005296:Ferrous Compounds / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005841:Gentisates / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000096:biosynthesis* / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010084:Oxidation-Reduction
chemical_list: D000975:Antioxidants; D001391:Azo Compounds; D002614:Chelating Agents; D002788:Cholesterol Esters; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D005841:Gentisates; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D009570:Nitriles; C109522:V 70; C020748:ferrous sulfate; D001241:Aspirin; C010925:2,5-dihydroxybenzoic acid