Functional evidence for anti-oxidant action of fluvastatin on low-density lipoprotein using isolated macrophages and aorta

Citation
S. Kagota et al., Functional evidence for anti-oxidant action of fluvastatin on low-density lipoprotein using isolated macrophages and aorta, CLIN EXP PH, 27(5-6), 2000, pp. 401-405
Citations number
28
Categorie Soggetti
Pharmacology & Toxicology
Journal title
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
ISSN journal
03051870 → ACNP
Volume
27
Issue
5-6
Year of publication
2000
Pages
401 - 405
Database
ISI
SICI code
0305-1870(200005/06)27:5-6<401:FEFAAO>2.0.ZU;2-B
Abstract
1. Fluvastatin has been reported to have not only a hypocholesterolaemic ef fect, but also a protective effect on low-density lipoprotein (LDL) from ox idation, We functionally evaluated the anti-oxidant effect of fluvastatin o n oxidation of LDL by copper ions in vitro using mouse macrophages and rabb it aorta preparations. 2. After native LDL (N-LDL) from rabbit plasma had been pre-incubated in th e presence or absence of fluvastatin (10 mu mol/L) for 4 h, the N-LDL, was mildly oxidized by incubation with 5 mu mol/L CuCl2 for 5 h and two oxidize d LDL, fluvastatin-pretreated (Flu-OxLDL) and -non-treated (OxLDL), were pr epared, The level of thiobarbituric acid-reactive substances (TBARS) in Flu -OxLDL and OxLDL markedly increased compared with N-LDL, The degree of incr ement was significantly less in Flu-ORI,DI, than OxLDL. 3. When macrophages were incubated with Flu-OxLDL or OxLDL, the amount of c holesteryl ester that accumulated in the macrophages markedly increased com pared with N-LDL, The degree of increment was significantly less in Flu-OxL DL than OxLDL. 4. Acetylcholine-induced endothelium-dependent relaxations i n 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 TEARS level, facilitated cholesteryl ester accumulation in macrophages and impaired endothelium-dependent relaxation elicited by OxLD L were not affected by simultaneous treatment with fluvastatin (10 mu mol/L ). 6. These findings indicate that fluvastatin can protect plasma LDL from oxi dative modification and, thereby, prevent cholesterol accumulation in macro phages and endothelial dysfunction in blood vessels. This additional anti-o xidative effect of fluvastatin may he beneficial for preventing the progres sion of atherosclerosis.