Inhibitory effects of fluvastain and its metabolites on the formation of several reactive oxygen species.
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 (1O2), superoxide anion (O2-), hydroxy radical (*OH), hypochlorite ion (OCL-), and linoleic acid peroxide (LOO*). Inhibitory effects of pravastatin (PV), simvastatin (SV), probucol (PR) and alpha-tocopherol (TOC) were also tested. The inhibitory effects of 5-hydroxy FV (M-2) and 6-hydroxy FV (M-3) on the formation of 1O2, O2-, *OH, and OCL- were strongest. Scavenging of 1O2 by M-4, M-5, (+)-FV, and (-)-FV was also noted. The inhibitory effects of (+)-FV on the formation of 1O2 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.
Nakashima
A
A
Tsukuba Research Institute, Novartis Pharma K.K., Ibaraki, Japan. akinori.nakashima@pharma.novartis.com
Ohtawa
M
M
Iwasaki
K
K
Wada
M
M
Kuroda
N
N
Nakashima
K
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism / Q000494:pharmacology*; D000077340:Fluvastatin; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology; D011341:Probucol / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology; D026082:Singlet Oxygen; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D005229:Fatty Acids, Monounsaturated; D016166:Free Radical Scavengers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D017382:Reactive Oxygen Species; D014810:Vitamin E; D026082:Singlet Oxygen; D000077340:Fluvastatin; D019821:Simvastatin; D017035:Pravastatin; D011341:Probucol; D010100:Oxygen