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

The antioxidative effect of fluvastatin sodium (fluvastatin), a 3-hydroxy-3 -methylglutaryl coenzyme A reductase inhibitor, on lipid peroxidation of ph osphatidylcholine (PC) liposomes was investigated in various peroxidizing s ystems. 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 th e peroxidation was: butylated hydroxytoluene > fluvastatin greater than or equal to probucol much greater than pravastatin. Moreover, concentrations o f fluvastatin ranging from 1 x 10(-6) to 1 x 10(-4) M inhibited peroxyl rad ical-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-dimethytvaleronitrile), respectively. However, pravas tatin 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 antioxida tive effects of fluvastatin may be due to the scavenging action of fluvasta tin on liposomal lipid peroxidation induced by peroxyl radicals generated i n the aqueous and lipid phases.