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- Miyajima Atsushi
- Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science
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- Amano Yasuha
- Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science
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- Kamamoto Takeyoshi
- Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science
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- Okamoto Masahiro
- Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science
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- Hirota Takashi
- Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science
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抄録
A selective cylooxygenase-2 (COX-2) inhibitor, rofecoxib, was withdrawn from the worldwide market due to an increased risk of cardiovascular (CV) events. A hypothesis has been proposed that rofecoxib promotes lipid oxidation, which increases the risk of CV events. However, this hypothesis was only predicated on in vitro experiments using isolated human low density lipoprotein and diluted human plasma. In the present study we investigated the effect of rofecoxib on the in vitro and in vivo production of thiorbarbituric acid reacting substance (TBARS) as an indicator of oxidation in plasma and aortas in rats. In vitro experiment, the TBARS production in plasma and aortic homogenate was not changed by the addition of rofecoxib at 2 µM, which concentration is around the maximum plasma concentration at clinical doses, or even at 200 µM. In addition, the production was not increased by rofecoxib in the presence of FeSO4 as a typical oxidant. Meanwhile the TBARS production in the aorta of rats after 4-weeks administration of 10 mg/kg/day rofecoxib was comparable to that of the control rats. These results in-vitro and in-vivo experiments suggest that rofecoxib would have no or very weak effect on lipid oxidation in clinical usage, and it is thought that the increase of CV events already reported stemmed from causes other than oxidative stress.
収録刊行物
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- Fundamental Toxicological Sciences
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Fundamental Toxicological Sciences 2 (4), 155-159, 2015
一般社団法人 日本毒性学会
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詳細情報
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- CRID
- 1390282680739493888
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- NII論文ID
- 130005097697
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- ISSN
- 2189115X
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
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- 抄録ライセンスフラグ
- 使用不可