EPR studies on hydroxyl radical-scavenging activities of pravastatin and fluvastatin

Abstract

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.

Reversal effect of simvastatin on the decrease in cannabinoid receptor 1 density in 6-hydroxydopamine lesioned rat brains

“…Our result was consistent with previous studies, showing the down-regulation of CB1 expression in a wide range of brain regions [47,53]. However different findings were also observed; such as an elevation in CB1 receptor mRNA expression [41], up-regulation in CB1 binding [27], or no change identified [28].…”

“…This subsequently causes excessive glutamate Simvastatin blocks important isoprenoid intermediates that would cause the release of specific microglia and pro-inflammatory cytokines [46,26]. Simvastatin has also been found to have anti-oxidant properties that may lower the level of reactive oxygen species [26,53,54]. and excitotoxicity towards substantia nigra pars reticulata (SNr) and medial globus pallidus (GPm) [4].…”

Statins inhibit expression of Thioredoxin reductase 1 in rat and human liver and reduce tumour development

“…As discussed more thoroughly in Paper III, the antioxidative capacity of fluvastatin has been reported by others in other model systems, such as human aortic smooth muscle cells [173] and on the plasma lipids of hyperlipidemic subjects [174]. This is proposed to be a consequence of its unique structure compared to other statins, giving it a free radical-scavenging activity against the superoxide anion and hydroxyl radical [175,176] that is independent of its HMG-CoA reductase inhibition capacity [177].…”

Ball-milled magnetite for efficient arsenic decontamination: Insights into oxidation–adsorption mechanism

“…The O2•functioned as an effective oxidizing agent for H2O and catalyzed the formation of H2O2 that further reacted with free electrons to generate •OH (Eqs. 12-13) (Vandjelovic et al, 2012). Significantly, the signal intensity of DMPO-OH was higher for Mm than for M0.…”