Intestinal Ischemia-Reperfusion Increases Efflux for Uric Acid Via Paracellular Route in the Intestine, but Decreases that Via Transcellular Route Mediated by BCRP

Authors

  • Jiro Ogura
  • Kaori Kuwayama
  • Atsushi Takaya
  • Yusuke Terada
  • Takashi Tsujimoto
  • Takahiro Koizumi
  • Hajime Maruyama
  • Asuka Fujikawa
  • Natsuko Takahashi
  • Masaki Kobayashi
  • Shirou Itagaki
  • Takeshi Hirano
  • Hiroaki Yamaguchi
  • Ken Iseki

DOI:

https://doi.org/10.18433/J3W896

Abstract

Purpose. Uric acid is thought to be one of the most important antioxidants in human biological fluids. Intestinal ischemia-reperfusion (I/R) is an important factor associated with high rates of morbidity and mortality. Reactive oxygen species (ROS) are responsible for intestinal I/R injury. The aim of this study was to clarify the efflux for uric acid from the intestine after intestinal I/R. Methods. We used intestinal ischemia-reperfusion (I/R) model rats. Serosal to mucosal flux for [14C]-uric acid was assessed by using Ussing-type diffusion chambers. BCRP/Bcrp expression was assessed by Western blot analysis. Caco-2 cells were used for a model of the intestinal epithelium, and rotenone was used as a mitochondrial dysfunction inducer. Results. Serosal to mucosal flux for uric acid was increased after intestinal I/R, and that for mannitol was also increased. Ko143, which is a BCRP inhibitor, did not affect the uric acid transport. The decreasing uric acid transport mediated by Bcrp was caused by decrease in the level of Bcrp homodimer, bridged by an S-S bond. The suppression of Bcrp S-S bond formation was associated with mitochondrial dysfunction. Moreover, BCRP S-S bond formation activity was decreased by rotenone in Caco-2 cells. Conclusions. Serosal to mucosal flux for uric acid is significantly increased via the paracelluler route, but that via the transcellular route mediated by Bcrp is decreased after intestinal I/R. The decreasing uric acid flux mediated by Bcrp is caused by suppression of Bcrp S-S bond formation. This suppression of Bcrp S-S bond formation may be related to mitochondrial dysfunction. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Published

2012-04-26

How to Cite

Ogura, J., Kuwayama, K., Takaya, A., Terada, Y., Tsujimoto, T., Koizumi, T., … Iseki, K. (2012). Intestinal Ischemia-Reperfusion Increases Efflux for Uric Acid Via Paracellular Route in the Intestine, but Decreases that Via Transcellular Route Mediated by BCRP. Journal of Pharmacy & Pharmaceutical Sciences, 15(2), 295–304. https://doi.org/10.18433/J3W896

Issue

Section

Pharmaceutical Sciences; Review Articles