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Intestinal P-glycoprotein Expression is Multimodally Regulated by Intestinal Ischemia-Reperfusion

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Title: Intestinal P-glycoprotein Expression is Multimodally Regulated by Intestinal Ischemia-Reperfusion
Authors: Terada, Yusuke Browse this author
Ogura, Jiro Browse this author →KAKEN DB
Tsujimoto, Takashi Browse this author
Kuwayama, Kaori Browse this author
Koizumi, Takahiro Browse this author
Sasaki, Shunichi Browse this author
Maruyama, Hajime Browse this author
Kobayashi, Masaki Browse this author →KAKEN DB
Yamaguchi, Hiroaki Browse this author →KAKEN DB
Iseki, Ken Browse this author →KAKEN DB
Issue Date: 2014
Publisher: Canadian Society for Pharmaceutical Sciences
Journal Title: Journal of pharmacy and pharmaceutical sciences
Volume: 17
Issue: 2
Start Page: 266
End Page: 276
PMID: 24934555
Abstract: Purpose. Reactive oxygen species (ROS) have multiple physiological effects that are amount-dependent. ROS are one of the causes of intestinal ischemia-reperfusion (I/R) injury. In this study, we investigated whether the amount of ROS and the degree of intestinal I/R injury affect the expression level of P-glycoprotein (P-gp). Methods. We used hydrogen peroxide (H2O2) as ROS in in vitro experiments. Intestinal I/R model rats, which were subjected 15-min ischemia (I/R-15), were used in in vivo experiments. Results. P-gp expression in Caco-2 cells was increased in response to 1 mu M of H2O2 but decreased upon exposure to 10 mM of H2O2. We previously reported that P-gp expression is decreased after intestinal I/R with 30-min ischemia (I/R-30), which time a large amount of ROS is generated. I/R-15 induced slightly less mucosal and oxidative injury than did I/R-30. P-gp expression in the jejunum was increased at 1 h after I/R-15, and ileal paracellular permeability was increased. The blood concentration of tacrolimus, a P-gp substrate, was lower during 0-20 min but was higher during 40-90 min post-administration compared with that in the sham-operated rats. P-gp expression in the ileum was decreased at 6 h after I/R-15, due to abnormal localization of P-gp, resulting in a high blood tacrolimus concentration in rats reperfused for 6 h. Conclusions. ROS multimodally regulate P-gp expression depending on its amount. This is important for understanding the pattern of P-gp expression after intestinal I/R.
Type: article
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: 小倉 次郎

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