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
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.