Antioxidative Effects of Fluvastatin, and Its Major Metabolites [II]

Akinori NAKASHIMA, Masakatsu OHTAWA, Naoki MASUDA, Hiroshi MORIKAWA, Kazuhide IWASAKI
2001 Yakugaku zasshi  
We investigated the antioxidative eŠects of ‰uvastatin (FV or (±)-FV), each enantiomer ((+)-FV, (-)-FV) and its major metabolites on lipid peroxidation using rat and human liver microsomes. The extent of NADPH induced microsomal (Ms) lipid peroxidation was determined by thiobarbituric acid (TBA) assay. The antioxidative eŠect of each compound was shown as the percentage of inhibition on the formation of TBA reactive substance (TBARS) against vehicle control. The antioxidative eŠects of
more » ... opherol (Toc), a potent antioxidative vitamin, probucol (PR), a potent antioxidative drug, pravastatin (PV) and simvastatin (SV), HMG-CoA reductase inhibitors, were also tested. The (±)-FV inhibit the formation of TBARS by 40 to 70% depending on Ms concentrations. The antioxidative eŠects of PR and TOC were comparable to those of FV. The inhibitory eŠects of PV and SV on the formation of TBARS were less potent than (±)-FV, PR and TOC. (+)-FV, (-)-FV, and (±)-FV inhibited the formation of TBARS by approximately 50 % using rat hepatic microsomes. The antioxidative eŠects of (+)-FV was comparable to that of (-)-FV using human hepatic microsomes. These results indicated that the antioxidative eŠects of (+)-FV were comparable to those of (-)-FV, although the HMG-CoA reductase inhibitory activity of (+)-FV was 30-fold higher than that of (-)-FV.
doi:10.1248/yakushi.121.113 pmid:11201159 fatcat:6l2lfegjnjgapnadepkadoivim