EPR studies on hydroxyl radical-scavenging activities of pravastatin and fluvastatin.
Statins are known clinically by their cholesterol reduction properties through the inhibition of HMG-CoA reductase. There is mounting evidence suggesting a protective role of statins in certain types of cancer, cardiac, and vascular disease through a mechanism that extends beyond their lipid lowering ability. The root mechanism of damage likely involves the inflammatory cascade, specifically compounds known as reactive oxygen species such as the hydroxyl radical. However, direct evidence for the hydroxyl-scavenging capacity of pravastatin and fluvastatin, two forms of statins being widely used to lower LDL cholesterol, is still lacking in literature. In this study, electron paramagnetic resonance spectroscopy in combination with 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-spin-trapping technique was utilized to determine the abilities of pravastatin and fluvastatin in scavenging hydroxyl radical generated from Fe(II) with H(2)O(2) system. In addition, we examined the effects of pravastatin and fluvastatin on oxidative-induced φX-174 RF I plasmid DNA damage. We have demonstrated here for the first time that pravastatin and fluvastatin at physiologically relevant concentrations significantly decreased formation of DMPO-OH adduct indicating that both compounds could directly scavenge hydroxyl radicals. However, pravastatin and fluvastatin were not able to directly protect against oxidative DNA plasmid damage. The hydroxyl radical sequestering ability of pravastatin and fluvastatin reported in this study may contribute to their beneficial use in certain types of cancer and in cardiovascular disease.
Division of Biomedical Sciences, Virginia Tech Corporate Research Center, Edward Via College of Osteopathic Medicine, 2265 Kraft Drive, Blacksburg, VA 24060, USA.
Nathan
N
Vandjelovic
Hong
H
Zhu
Hara P
HP
Misra
Ryan P
RP
Zimmerman
Zhenquan
Z
Jia
Yunbo
Y
Li
D053960:DNA Breaks / Q000187:drug effects*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000494:pharmacology; D000077340:Fluvastatin; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000737:chemistry / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects / Q000235:genetics; D017035:Pravastatin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D019097:Spin Trapping / Q000379:methods
D005229:Fatty Acids, Monounsaturated; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D000077340:Fluvastatin; D006861:Hydrogen Peroxide; D017035:Pravastatin