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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. |
Rights: | http://creativecommons.org/licenses/by-sa/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/57655 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 小倉 次郎
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