Protective effect of fluvastatin on degradation of apolipoprotein B by a radical reaction in human plasma

Fluvastatin, which is a synthetic 3-hydroxy-3-methylglutaryl coenzyme (HMG- CoA) reductase inhibitor, its metabolites (M2, M3 and M4) and trolox all in hibited the decrease of apolipoprotein B-100 (apoB) and alpha -tocopherol i n a radical reaction of human plasma initiated by Cu2+. The concentrations of fluvastatin, M2, M3, M4 and trolox for 50% inhibition (IC50) of apoB fra gmentation were 405, 8.55, 1.75, 305, and 43.4 muM, respectively. The IC50 value of pravastatin, which is another HMG-CoA reductase inhibitor, was 288 0 muM, showing that pravastatin is not an effective antioxidant. Although f luvastatin, its metabolites and trolox inhibited the decrease of alpha -toc opherol in a similar manner to that of apoB, pravastatin did not significan tly inhibit the decrease of a; tocopherol. Since oxidation of low density l ipoprotein (LDL) is an important step in the initiation and progression of atherosclerosis, fluvastatin may reduce the risk of atherosclerosis not onl y by lowering plasma cholesterol but also by protecting LDL from oxidation.