Cellular Physiology and Biochemistry (Oct 2013)

MDR1 is Related to Intestinal Epithelial Injury Induced by Acetylsalicylic Acid

  • 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

DOI
https://doi.org/10.1159/000354497
Journal volume & issue
Vol. 32, no. 4
pp. 942 – 950

Abstract

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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.

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