Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors.

Abstract

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used for preventing cardiovascular and cerebrovascular diseases by controlling blood cholesterol level. Additionally, previous studies revealed the scavenging effects of statins on free radicals. We assessed direct scavenging activities of two water-soluble statins, fluvastatin and pravastatin, on multiple free radicals using electron spin resonance spectrometry with spin trapping method. We estimated reaction rate constants (kfv for fluvastatin, and kpv for pravastatin). Superoxide anion was scavenged by fluvastatin and pravastatin with kfv and kpv of 4.82 M−1s−1 and 49.0 M−1s−1, respectively. Scavenging effects of fluvastatin and pravastatin on hydroxyl radical were comparable; both kfv and kpv were >109 M−1s−1. Fluvastatin also eliminated tert-butyl peroxyl radical with relative kfv of 2.63 to that of CYPMPO, whereas pravastatin did not affect tert-butyl peroxyl radical. Nitric oxide was scavenged by fluvastatin and pravastatin with kfv and kpv of 68.6 M−1s−1 and 701 M−1s−1, respectively. Both fluvastatin and pravastatin had scavenging effects on superoxide anion, hydroxyl radical and nitric oxide radical. On the other hand, tert-butyl peroxyl radical was scavenged only by fluvastatin, suggesting that fluvastatin might have more potential effect than pravastatin to prevent atherosclerosis and ischemia/reperfusion injury via inhibiting oxidation of lipids.