Mechanism of Antioxidative Activity of Fluvastatin-Determination of the Active Position.

Nakamura, Takashi; Nishi, Hiroyuki; Kokusenya, Yoshio; Hirota, Kenichi; Miura, Yozo

doi:10.1248/cpb.48.235

Cited by 35 publications

(21 citation statements)

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“…21 The antioxidant action of statins is derived not only from the reduction of oxidized low-density lipoprotein, but from inhibition of NADPH oxidase, which generates superoxide anion (·O2 -) in the vascular wall. 22 FV has a potent antioxidant property as a free radical scavenger, because of its unique chemical structure, 17 but in the present study, however, FV did not reduce the myocardial content of 8-OHdG, which is produced by hydroxylation at the C-8 position of deoxyguanosine by ·OH and is currently used as a stable biomarker of oxidative DNA damage. 18,23 Formation of 8-OHdG in the heart with IR progressively increases after reperfusion and is completely blocked by co-treatment with a free radical scavenger.…”

Section: Antioxidant Property Of Fvcontrasting

confidence: 72%

“…13 Statins are known to decrease free radical generation in the vascular wall 14,15 and myocardium, 16 which suggests that statins may protect the ischemic myocardium from IR injury via suppression of oxygen-derived free radicals produced upon reperfusion. Among the statins, fluvastatin (FV) has a potent free radical scavenging property derived from its chemical structure 17 and the purpose of the present study was to elucidate the effects of acute administration of FV and the role of its antioxidant property on IR injury in rats. …”

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confidence: 99%

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Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Matsuki

Igawa

Nozawa

et al. 2006

Circ J

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arly reperfusion of an occluded coronary artery preserves myocardial viability and function by limiting the size of the myocardial infarct. 1,2 However, despite early reperfusion, myocardial ischemia-reperfusion (IR) injuries, including no reflow, stunning and reperfusion arrhythmias, sometimes occur, thereby attenuating the cardioprotective effect of reperfusion therapy. 3 Recent studies in experimental animals have demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) attenuate IR injury independently of their lipid-lowering action. [4][5][6][7][8] Statins have pleiotropic effects, including improvement of endothelial function by increased nitric oxide (NO) bioavailability, 9 and antioxidant 10 and antiinflammatory actions, 11 which may explain their attenuation of IR injury. The experimental result of cardioprotection by statins has therapeutic implication for patients with acute coronary syndrome who will be treated with reperfusion therapy; however, the time at which statin treatment was administered before IR varied from hours to days, and the Circulation Journal Vol.70, December 2006 results are conflicting. 5,12 It is not clear whether acute administration of statins at the onset of ischemia or reperfusion will prevent or attenuate the IR injury.Oxidative stress plays an important role in IR injury, and antioxidants such as superoxide dismutase and catalase could limit the infarct size in IR. 13 Statins are known to decrease free radical generation in the vascular wall 14,15 and myocardium, 16 which suggests that statins may protect the ischemic myocardium from IR injury via suppression of oxygen-derived free radicals produced upon reperfusion. Among the statins, fluvastatin (FV) has a potent free radical scavenging property derived from its chemical structure 17 and the purpose of the present study was to elucidate the effects of acute administration of FV and the role of its antioxidant property on IR injury in rats. MethodsThe experimental procedures followed the approved guidelines for animal experimentation at the University of Toyama. Myocardial IRMale Wistar rats weighing 270-380 g (n=103) were intubated under ether anesthesia and ventilated using a rodent respirator. The heart was exposed by left thoracotomy and the left coronary artery was ligated 2-3 mm from its origin Background Three-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are known to attenuate myocardial ischemia-reperfusion (IR) injury. Fluvastatin (FV) has a potent free radical scavenging action, but it is unclear whether the timing of FV administration could affect its cardioprotective effect or if the antioxidant property of FV might attenuate IR injury. Methods and Results IR was induced in rats by left coronary artery occlusion for 30 min followed by 24-h reperfusion. The rats were divided into 4 groups: oral FV group (10 mg/kg per day for 2 weeks before ischemia); iv, FV group (10 mg/kg) before ischemia; iv, FV group (10 mg/kg) before reperfusion; and control gr...

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Section: Antioxidant Property Of Fvcontrasting

confidence: 72%

mentioning

confidence: 99%

Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Matsuki

Igawa

Nozawa

et al. 2006

Circ J

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“…12,13 The mechanism of the distinct antioxidative properties of fluvastatin are found to be through its characteristic structure. 36 In addition, in vivo studies have demonstrated that fluvastatin inhibited the manifestation of the atherosclerotic features through its antioxidative effect, independently of the lipid-lowering effect. 14,15 As prevalent mild-to-moderate hyperhomocysteinemia plays an important role in the onset and/or progression of atherosclerosis through the oxidative stress mechanism, the administration of antioxidant fluvastatin can be expected as a future anti-atherosclerotic therapy.…”

Section: Discussionmentioning

confidence: 99%

Fluvastatin Ameliorates the Hyperhomocysteinemia-Induced Endothelial Dysfunction-The Antioxidative Properties of Fluvastatin-

Morita

Saito

Ohashi

et al. 2005

Circ J

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“…The higher antioxidant activity of simvastatin when compared with atorvastatin may be related to its phenolic hydroxyl group. Nakamura et al (2000) reported the mechanism of the antioxidant activity of fluvastatin and its metabolites due to the presence of the phenolic hydroxyl group.…”

Section: Resultsmentioning

confidence: 99%

Anin Vitro. Comparative Study on the Antioxidant Activity and Determination of Antibacterial Potential of Atorvastatin and Simvastatin

Ajith

Divya

2007

Pharmaceutical Biology

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Free radicals generated from oxidative stress (OS) have been depicted in the causation of cancerous and noncancerous diseases in humans. Increase in fat content of the body may favor the deleterious effect of free radical attack. The generation of free radicals is enhanced in respiratory burst during bacterial infection. The level of plasma membrane cholesterol appears to be critical in the regulation of microbial entry, intracellular trafficking, and exit. The current study was designed to compare the in vitro antibacterial and antioxidant activities of hypocholesterolemic drugs atorvastatin and simvastatin. Agar-well diffusion assay was used to screen the antibacterial activity using Gram-positive and Gram-negative bacterial strains. Antioxidant activity was evaluated using Fe 2þ -induced lipid peroxidation inhibiting activity in whole rat liver homogenate and Fe 3þ reducing activity using ferric-reducing antioxidant power (FRAP) assay. Atorvastatin and simvastatin inhibited the growth of all bacterial strains tested. The zone of inhibition produced by atorvastatin is higher than that of simvastatin. However, antioxidant activities of simvastatin were higher than those of atorvastatin. The exhibited pleiotropic activities of these statins suggest their clinical advantages against bacterial infection and oxidative stress-induced human ailments apart from their wide use for hypolipidemic effects.

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Mechanism of Antioxidative Activity of Fluvastatin-Determination of the Active Position.

Cited by 35 publications

References 0 publications

Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Early Administration of Fluvastatin, but not at the Onset of Ischemia or Reperfusion, Attenuates Myocardial Ischemia-Reperfusion Injury Through the Nitric Oxide Pathway Rather Than Its Antioxidant Property

Fluvastatin Ameliorates the Hyperhomocysteinemia-Induced Endothelial Dysfunction-The Antioxidative Properties of Fluvastatin-

Anin Vitro. Comparative Study on the Antioxidant Activity and Determination of Antibacterial Potential of Atorvastatin and Simvastatin

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