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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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Title: Effect of oxidative stress on expression and function of human and rat organic anion transporting polypeptides in the liver
Authors: Tsujimoto, Takashi Browse this author
Ogura, Jiro Browse this author →KAKEN DB
Kuwayama, Kaori Browse this author
Koizumi, Takahiro Browse this author
Sasaki, Shunichi Browse this author
Terada, Yusuke Browse this author
Kobayashi, Masaki Browse this author →KAKEN DB
Yamaguchi, Hiroaki Browse this author →KAKEN DB
Iseki, Ken Browse this author →KAKEN DB
Keywords: Organic anion transporting polypeptide
Hydrogen peroxide
Oxidative stress
Pharmacokinetics
Issue Date: 31-Dec-2013
Publisher: Elsevier science bv
Journal Title: International journal of pharmaceutics
Volume: 458
Issue: 2
Start Page: 262
End Page: 271
Publisher DOI: 10.1016/j.ijpharm.2013.10.013
PMID: 24409515
Abstract: 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.
Type: article (author version)
URI: http://hdl.handle.net/2115/54673
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 井関 健

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