Direct Radical Scavenging Activity of Benzbromarone Provides Beneficial Antioxidant Properties for Hyperuricemia Treatment
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- Kadowaki Daisuke
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University Center for Clinical Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University
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- Sakaguchi Shoichi
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University
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- Miyamoto Yohei
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
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- Taguchi Kazuaki
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University Faculty of Pharmaceutical Sciences, Sojo University
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- Muraya Nanako
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University
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- Narita Yuki
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University Center for Clinical Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University
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- Sato Keizo
- School of Pharmacy, Kyushu University of Health and Welfare
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- Chuang Victor Tuan Giam
- School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University
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- Maruyama Toru
- Center for Clinical Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
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- Otagiri Masaki
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University Faculty of Pharmaceutical Sciences, Sojo University
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- Hirata Sumio
- Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University Center for Clinical Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kumamoto University
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Abstract
Uric acid exerts an important antioxidant effect against external oxidative stress under physiological conditions. However, uric acid itself can increase oxidative stress via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation in adipocytes and vascular cells. Uric acid transporter 1 is involved in the generation of this oxidative stress. Furthermore, uric acid locally activates the renin–angiotensin system, thus producing angiotensin II and subsequently increasing intracellular oxidative stress. Benzbromarone has been reported to suppress uric acid reabsorption via uric acid transporter 1 inhibition in renal tubular cells. In this study we evaluated the in vitro antioxidant effect of benzbromarone from several perspectives. First, the direct radical-trapping capacity of benzbromarone was measured by chemiluminescence assay and electron paramagnetic resonance spectroscopy. Second, the intracellular antioxidant activity of benzbromarone in hyperuricemia was evaluated using endothelial cells. In light of these results, benzbromarone is hypothesized directly to scavenge the superoxide anion radical. In addition, benzbromarone inhibited reactive oxygen species production that was induced by angiotensin II or uric acid in endothelial cells. These findings suggest that benzbromarone possesses the ability directly to scavenge radicals and may act as an antioxidant against uric acid and angiotensin II-induced oxidative stresses in endothelial cells at therapeutically achievable levels in blood.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 38 (3), 487-492, 2015
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204634522752
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- NII Article ID
- 130004872274
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- NII Book ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 026193375
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- PubMed
- 25757933
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed