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Functional Evidence For Anti‐Oxidant Action Of Fluvastatin On Low‐Density Lipoprotein Using Isolated Macrophages And Aorta
Author(s) -
Kagota Satomi,
Yamaguchi Yu,
Nakamura Kazuki,
Kunitomo Masaru
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03246.x
Subject(s) - fluvastatin , tbars , chemistry , endocrinology , thiobarbituric acid , medicine , lipoprotein , low density lipoprotein , cholesterol , in vitro , lipid peroxidation , pharmacology , oxidative stress , biochemistry , simvastatin
SUMMARY 1. Fluvastatin has been reported to have not only a hypocholesterolaemic effect, but also a protective effect on low‐ density lipoprotein (LDL) from oxidation. We functionally evaluated the anti‐oxidant effect of fluvastatin on oxidation of LDL by copper ions in vitro using mouse macrophages and rabbit aorta preparations. 2. After native LDL (N‐LDL) from rabbit plasma had been pre‐incubated in the presence or absence of fluvastatin (10 μmol/L) for 4 h, the N‐LDL was mildly oxidized by incubation with 5 μmol/L CuCl 2 for 5 h and two oxidized LDL, fluvastatin‐pretreated (Flu‐OxLDL) and ‐non‐treated (OxLDL), were prepared. The level of thiobarbituric acid‐reactive substances (TBARS) in Flu‐OxLDL and OxLDL markedly increased compared with N‐LDL. The degree of increment was significantly less in Flu‐OxLDL than OxLDL. 3. When macrophages were incubated with Flu‐OxLDL or OxLDL, the amount of cholesteryl ester that accumulated in the macrophages markedly increased compared with N‐LDL. The degree of increment was significantly less in Flu‐OxLDL than OxLDL. 4. Acetylcholine‐induced endothelium‐dependent relaxations in rabbit aortic rings were impaired in the presence of either Flu‐OxLDL or OxLDL. The degree of impairment was significantly less in Flu‐OxLDL. 5. The increased TBARS level, facilitated cholesteryl ester accumulation in macrophages and impaired endothelium‐dependent relaxation elicited by OxLDL were not affected by simultaneous treatment with fluvastatin (10 μmol/L). 6. These findings indicate that fluvastatin can protect plasma LDL from oxidative modification and, thereby, prevent cholesterol accumulation in macrophages and endothelial dysfunction in blood vessels. This additional anti‐oxidative effect of fluvastatin may be beneficial for preventing the progression of atherosclerosis.