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MDR1 is Related to Intestinal Epithelial Injury Induced by Acetylsalicylic Acid

Authors :
Munehiro Kugai
Kazuhiko Uchiyama
Toshifumi Tsuji
Hiroyuki Yoriki
Akifumi Fukui
Ying Qin
Yasuki Higashimura
Katsura Mizushima
Naohisa Yoshida
Kazuhiro Katada
Kazuhiro Kamada
Osamu Handa
Tomohisa Takagi
Hideyuki Konishi
Nobuaki Yagi
Toshikazu Yoshikawa
Yoshiyuki Shirasaka
Ikumi Tamai
Yuji Naito
Yoshito Itoh
Source :
Cellular Physiology and Biochemistry, Vol 32, Iss 4, Pp 942-950 (2013)
Publication Year :
2013
Publisher :
Cell Physiol Biochem Press GmbH & Co KG, 2013.

Abstract

Background/Aims: Although the cytotoxicity of aspirin against the intestinal epithelium is a major clinical problem, little is known about its pathogenesis. We assessed the involvement of Multi Drug Resistance (MDR) 1 in intestinal epithelial cell injury caused by aspirin using MDR1 gene-transfected Caco2 cells. Methods: Caco2 cells were treated with various concentrations of aspirin for 24 h. After treatment of Caco2 cells with verapamil, a specific inhibitor of MDR1, we assessed the extent of cell injury using a WST-8 assay at 24 h after aspirin-stimulation. We performed the same procedure in MDR1 gene-transfected Caco2 cells. To determine the function of MDR1 in the metabolism of aspirin, flux study was performed using 14C-labeled aspirin. Results: The level of aspirin-induced cell injury was higher in verapamil-treated Caco2 cells than in control cells and was less serious in MDR1-transfected Caco2 cells than in control vector-transfected cells. The efflux of 14C-labeled aspirin was higher in verapamil-treated Caco2 cells than in control cells. Conclusion: These data suggest that aspirin effux occurs through the MDR1 transporter and that the MDR1 transporter is involved in the pathogenesis of aspirin-induced cell injury.

Details

Language :
English
ISSN :
10158987 and 14219778
Volume :
32
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Cellular Physiology and Biochemistry
Publication Type :
Academic Journal
Accession number :
edsdoj.12860c168a27475d8c128156f9a4553c
Document Type :
article
Full Text :
https://doi.org/10.1159/000354497