Antioxidative effect of fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on peroxidation of phospholipid liposomes.

Abstract

The antioxidative effect of fluvastatin sodium (fluvastatin), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on lipid peroxidation of phosphatidylcholine (PC) liposomes was investigated in various peroxidizing systems. Fluvastatin markedly inhibited the formation of thiobarbituric acid reactive substances in iron (II)-supported peroxidation of liposomes (IC50 = 1.2 x 10(-5) M). The order of magnitude of inhibition of each drug on the peroxidation was: butylated hydroxytoluene > fluvastatin > or = probucol >> pravastatin. Moreover, concentrations of fluvastatin ranging from 1 x 10(-6) to 1 x 10(-4) M inhibited peroxyl radical-mediated peroxidation of liposomes induced by water-soluble and lipid-soluble radical generators, 2,2'-azobis (2-amidinopropane) dihydro-chloride and 2,2'-azobis (2,4-dimethylvaleronitrile), respectively. However, pravastatin showed no effect against peroxyl radical-mediated peroxidation. These results indicate that fluvastatin acted non-enzymatically as an effective inhibitor against lipid peroxidation of PC liposomes and that the antioxidative effects of fluvastatin may be due to the scavenging action of fluvastatin on liposomal lipid peroxidation induced by peroxyl radicals generated in the aqueous and lipid phases.