Antioxidative effects of fluvastatin, and its major metabolites

Fluvastatin (FV) is a highly potent inhibitor of 3-hydroxy-3-methylgrutaryl -CoA (HMG-CoA) reductase. Recently, its antioxidant effect caused by inhibi ting the formation of low density lipoproteins (LDL) in vitro has been repo rted. In this study, we reported the antioxidant effects of FV and its majo r metabolites in human (M-2, M-3, M-4, M-5, and M-7) on lipid peroxidation using rat liver microsomes. The extent of NADPH- induced microsomal (Ms) li pid peroxidation was determined by the thiobarbituric acid (TBA) assay. The antioxidant effect of each compound was shown as the percentage of inhibit ion on the formation of TEA reactive substances (TBARS) against the vehicle control. Probucol (PR), a potent antioxidant drug, was used as a reference control. The concentration of each compound in this experiment was set at 0.1 mM (final cone.). FV inhibited the formation of TEARS by 30 to 60% with out depending on the used Ms concentrations (0.025-0.2 mg protein/ml). The antioxidant effects of M-2, M-3, and M-5 were comparable to that of FV at l ow Ms concentarations. At the highest Ms concentration, however, the antiox idant effects of these metabolites were considerably higher than that of FV . Inhibition of the formation of TEARS by M-4 or M-7 was approximately 30% of the control and independent of the used Ms concentrations. The antioxida nt effect of PR was comparable to those of M-2, M-3, and M-5 in this study. Pravastatin (PV), a potent inhibitor of HMG-CoA reductase, reduced the for mation of TEARS around 20% at 0.25 or 0.5 mg protein/ml of Ms concentration s. But the value of percentage of inhibition was around 5% at 0.1 or 0.2 mg protein/ml of Ms concentrations. In conclusion, the antioxidant effects of FV, M-2, M-3, and M-5 were found to be comparable to that of PR.