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Intestinal ischemia-reperfusion increases efflux for uric acid via paracellular route in the intestine, but decreases that via transcellular route mediated by BCRP.
J Pharm Pharm Sci. 2012; 15(2):295-304.JP

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.

Authors+Show Affiliations

Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22579008

Citation

Ogura, Jiro, et al. "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 : a Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques, vol. 15, no. 2, 2012, pp. 295-304.
Ogura J, Kuwayama K, Takaya A, et al. Intestinal ischemia-reperfusion increases efflux for uric acid via paracellular route in the intestine, but decreases that via transcellular route mediated by BCRP. J Pharm Pharm Sci. 2012;15(2):295-304.
Ogura, J., Kuwayama, K., Takaya, A., Terada, Y., Tsujimoto, T., Koizumi, T., Maruyama, H., Fujikawa, A., Takahashi, N., Kobayashi, M., Itagaki, S., Hirano, T., Yamaguchi, H., & 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 : a Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques, 15(2), 295-304.
Ogura J, et al. Intestinal Ischemia-reperfusion Increases Efflux for Uric Acid Via Paracellular Route in the Intestine, but Decreases That Via Transcellular Route Mediated By BCRP. J Pharm Pharm Sci. 2012;15(2):295-304. PubMed PMID: 22579008.
* Article titles in AMA citation format should be in sentence-case
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 -