Inhibitory effects of fluvastain and its metabolites on the formation of several reactive oxygen species

Abstract

We investigated the inhibitory effects of fluvastain (FV) and its metabolites (M-2, M-3, M-4, M-5, and M-7) on the formation of several reactive oxygen species (ROS), such as singlet oxygen ( 1O 2), superoxide anion (O 2 −), hydroxy radical (.OH), hypochlorite ion (OCL −, and linoleic acid peroxide (LOO.). Inhibitory effects of pravastatin (PV), simvastatin (SV), probucol (PR) and α-tocopherol (TOC) were also tested. The inhibitory effects of 5-hydroxy FV (M-2) and 6-hydroxy FV (M-3) on the formation of 1O 2, O 2 −, .OH, and OCL − were strongest. Scavenging of 1O 2 by M-4, M-5, (+)-FV, and (−)-FV was also noted. The inhibitory effects of (+)-FV on the formation of 1O 2 were comparable to those of (−)-FV. PV, SV, PR and M-7 had little or no inhibitory effect on the formation of several ROS. In conclusion, FV and its metabolites, particulary M-2 and M-3, have the potential to protect against oxidative stress mediated by several ROS.