1999 Volume 47 Issue 7 Pages 1010-1012
We investigated the in vitro hydroxyl radical scavengig activity of fluvastatin, a 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor. Fluvastain showed hydroxyl redical scavenging activity as potent as that of dimethylthiourea and α-tocopherol, which are well-known respectively, as a hydroxyl radical scavenger and a natural antioxidant. Since this effect was not observed in other HMG-CoA reductase inhibitors, such as pravastain and simvastatin, the scavenging effect of fluvastatin on hydroxyl radicals would not be a common property of HMG-CoA reductase inhibitors, but is derived from the unique chemical structure of fluvastatin. The hydroxyl radical scavenging activities of human metabolites of fluvastatin were also determined. All the tested metabolites possessing the fluorophenyl indole moiety showed activity. Among them, the metabolites which possess a phenolic hydroxyl group on the indole moiety showed stronger effects than that of fluvastatin. We suggest that the fluorophenyl indole moiety of fluvastatin is important for manifestation of the activity and that the phenolic hydroxyl group enhances the potency.
