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 inhibited the decrease of apolipoprotein B-100 (apoB) and alpha -tocopherol in a radical reaction of human plasma initiated by Cu2+. The concentrations of fluvastatin, M2, M3, M4 and trolox for 50% inhibition (IC50) of apoB fragmentation 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 2880 muM, showing that pravastatin is not an effective antioxidant. Although fluvastatin, its metabolites and trolox inhibited the decrease of alpha -tocopherol in a similar manner to that of apoB, pravastatin did not significantly inhibit the decrease of a; tocopherol. Since oxidation of low density lipoprotein (LDL) is an important step in the initiation and progression of atherosclerosis, fluvastatin may reduce the risk of atherosclerosis not only by lowering plasma cholesterol but also by protecting LDL from oxidation.