Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma.
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.
Ashidate
Keiko
K
Department of Internal Medicine, Kudanzaka Hospital, Tokyo, Japan.
Kawamura
Mitsunobu
M
Mimura
Daigo
D
Tohda
Hisako
H
Miyazaki
Shigeru
S
Teramoto
Tamio
T
Yamamoto
Yorihiro
Y
Hirata
Yukio
Y
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
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