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Effect of oxidative stress on expression and function of human and rat organic anion transporting polypeptides in the liver

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タイトル: Effect of oxidative stress on expression and function of human and rat organic anion transporting polypeptides in the liver
著者: Tsujimoto, Takashi 著作を一覧する
Ogura, Jiro 著作を一覧する
Kuwayama, Kaori 著作を一覧する
Koizumi, Takahiro 著作を一覧する
Sasaki, Shunichi 著作を一覧する
Terada, Yusuke 著作を一覧する
Kobayashi, Masaki 著作を一覧する
Yamaguchi, Hiroaki 著作を一覧する
Iseki, Ken 著作を一覧する
キーワード: Organic anion transporting polypeptide
Hydrogen peroxide
Oxidative stress
発行日: 2013年12月31日
出版者: Elsevier science bv
誌名: International journal of pharmaceutics
巻: 458
号: 2
開始ページ: 262
終了ページ: 271
出版社 DOI: 10.1016/j.ijpharm.2013.10.013
抄録: Reactive oxygen species (ROS) have physiological function and involve alteration of physical state. However, it is not clear effect of oxidative stress on pharmacokinetics. Organic anion transporting polypeptides (human: OATPs, rodent: Oatps) are important for uptake of endogenous and exogenous compounds into hepatocytes. Thus, alteration of OATPs/Oatps expression level may affect pharmacokinetics of various drugs. In this study, we investigated the alteration of OATPs/Oatps expression levels and function by oxidative stress, and the effect of alteration of those on pharmacokinetics of a typical OATPs/Oatps substrate pravastatin. OATPs/Oatps expression levels and function were altered by H2O2-induced oxidative stress in in vitro experiments. The alteration of Oatps expression by oxidative stress also occurred in in vivo experiments. Oatp1a1, Oatp1a4 and Oatp1b2 expression in the liver were decreased in rats fed powdery diet containing 2% inosine, which induces oxidative stress through activation of xanthine oxidase, for 1 day. The decrease in Oatps expression levels by oxidative stress caused the suppression of pravastatin uptake to the liver, and resulted in high plasma concentration of pravastatin and low biliary excretion. In conclusion, oxidative stress induces alteration of OATPs/Oatps expression and function in hepatocytes, resulting in alteration of pharmacokinetics of their substrates. (C) 2013 Elsevier B.V. All rights reserved.
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 井関 健


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