Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma

被引：75
作者：
Ashidate, K
Kawamura, M
Mimura, D
Tohda, H
Miyazaki, S
Teramoto, T
Yamamoto, Y
Hirata, Y
机构：
[1] Tokyo Teishin Hosp, Dept Internal Med, Chiyoda Ku, Tokyo 1028798, Japan
[2] Kudanzaka Hosp, Dept Internal Med, Tokyo, Japan
[3] Univ Tokyo, Grad Sch Engn, Dept Chem & Biotechnol, Tokyo, Japan
[4] Univ Tokyo, Sch Med, Dept Internal Med, Tokyo 113, Japan
[5] Tokyo Univ Technol, Sch Bion, Tokyo, Japan
[6] Tokyo Med & Dent Univ, Dept Clin & Mol Endocrinol, Tokyo, Japan
来源：
EUROPEAN JOURNAL OF PHARMACOLOGY | 2005年 / 513卷 / 03期
关键词：
gentisic acid; aspirin; antioxidant; LDL oxidation;
D O I：
10.1016/j.ejphar.2005.03.012
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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 (CoQH(2)-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. (c) 2005 Elsevier B.V. All rights reserved.
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收藏
页码：173 / 179
页数：7
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