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Antioxidative Effects of Fluvastatin on Superoxide Anion Activated by Angiotensin II in Human Aortic Smooth Muscle Cells

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Abstract

We examined the antioxidative effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), on superoxide anion formation activated by angiotensin II (Ang II) in vitro. The effects of fluvastatin were also compared to simvastatin and a water-soluble analog of α-tocopherol, trolox. Treatment of human aortic smooth muscle cells (hASMC) with Ang II for 24 hours resulted in a 3.2 ± 0.5-fold increase in intracellular superoxide anion formation as detected by lucigenin assay. hASMC treated with clinical concentrations of fluvastatin (0–100 nM) showed a dose-dependent decrease in Ang II-activated superoxide anion formation. The addition of similar concentrations of trolox to hASMC inhibited Ang II-activated superoxide anion formation in a dose-dependent manner. However, simvastatin at similar doses failed to inhibit Ang II-activated superoxide anion formation by hASMC. Our results indicate that in addition to its hypocholesterolemic effect, fluvastatin may have direct antioxidative effects, suggesting its possible protective effect on atherosclerotic process.

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Authors and Affiliations

  1. Department of Health and Social Welfare, Fukuoka College of Health Sciences, 2-15-1, Tamura, Sawara-Ku, 814-0193, Japan

    Mari Kugi

  2. Second Department of Internal Medicine, Faculty of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Akira Matsunaga & Kikuo Arakawa

  3. Department of Laboratory Medicine, Faculty of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Junko Ono

  4. Graduate School of Public Health Medicine, International University of Health and Welfare, 1-3-1, Nagahama Chuo-ku, Fukuoka, 810-0071, Japan

    Jun Sasaki

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  1. Mari Kugi
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  2. Akira Matsunaga
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  4. Kikuo Arakawa
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Kugi, M., Matsunaga, A., Ono, J. et al. Antioxidative Effects of Fluvastatin on Superoxide Anion Activated by Angiotensin II in Human Aortic Smooth Muscle Cells. Cardiovasc Drugs Ther 16, 203–207 (2002). https://doi.org/10.1023/A:1020692220701

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