TY - JOUR T1 - Intestinal ischemia-reperfusion increases efflux for uric acid via paracellular route in the intestine, but decreases that via transcellular route mediated by BCRP. AU - Ogura,Jiro, AU - Kuwayama,Kaori, AU - Takaya,Atsushi, AU - Terada,Yusuke, AU - Tsujimoto,Takashi, AU - Koizumi,Takahiro, AU - Maruyama,Hajime, AU - Fujikawa,Asuka, AU - Takahashi,Natsuko, AU - Kobayashi,Masaki, AU - Itagaki,Shirou, AU - Hirano,Takeshi, AU - Yamaguchi,Hiroaki, AU - Iseki,Ken, PY - 2012/5/15/entrez PY - 2012/5/15/pubmed PY - 2012/9/18/medline SP - 295 EP - 304 JF - Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques JO - J Pharm Pharm Sci VL - 15 IS - 2 N2 - 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. SN - 1482-1826 UR - https://www.unboundmedicine.com/medline/citation/22579008/Intestinal_ischemia_reperfusion_increases_efflux_for_uric_acid_via_paracellular_route_in_the_intestine_but_decreases_that_via_transcellular_route_mediated_by_BCRP_ L2 - http://ejournals.library.ualberta.ca/index.php/JPPS/article/view/12242/13663 DB - PRIME DP - Unbound Medicine ER -