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Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2
Open accessAbstract
Urinary excretion accounts for two-thirds of total elimination of uric acid and the remainder is excreted in feces. However, the mechanism of extra-renal elimination is poorly understood. In the present study, we aimed to clarify the mechanism and the extent of elimination of uric acid through liver and intestine using oxonate-treated rats and Caco-2 cells as a model of human intestinal epithelium. In oxonate-treated rats, significant amounts of externally administered and endogenous uric acid were recovered in the intestinal lumen, while biliary excretion was minimal. Accordingly, direct intestinal secretion was thought to be a substantial contributor to extra-renal elimination of uric acid. Since human efflux transporter BCRP/ABCG2 accepts uric acid as a substrate and genetic polymorphism causing a decrease of BCRP activity is known to be associated with hyperuricemia and gout, the contribution of rBcrp to intestinal secretion was examined. rBcrp was confirmed to transport uric acid in a membrane vesicle study, and intestinal regional differences of expression of rBcrp mRNA were well correlated with uric acid secretory activity into the intestinal lumen. Bcrp1 knockout mice exhibited significantly decreased intestinal secretion and an increased plasma concentration of uric acid. Furthermore, a Bcrp inhibitor, elacridar, caused a decrease of intestinal secretion of uric acid. In Caco-2 cells, uric acid showed a polarized flux from the basolateral to apical side, and this flux was almost abolished in the presence of elacridar. These results demonstrate that BCRP contributes at least in part to the intestinal excretion of uric acid as extra-renal elimination pathway in humans and rats.
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Matsuo, H., Takada, T., Ichida, K., Nakamura, T., Nakayama, A., Ikebuchi, Y., Ito, K., Kusanagi, Y., Chiba, T., Tadokoro, S., et al. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000237 · Cited by 437
Multiple organic anion transporters contribute to net renal excretion of uric acid
Eraly, S. A., Vallon, V., Rieg, T., Gangoiti, J. A., Wikoff, W. R., Siuzdak, G., Barshop, B. A., & Nigam, S. K. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.00207.2007 · Cited by 235
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Nigam, S. K. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4461 · Cited by 527
Uric acid and cardiovascular disease
Ndrepepa, G. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.05.046 · Cited by 498
Intestinal Microbiota Distinguish Gout Patients from Healthy Humans
Guo, Z., Zhang, J., Wang, Z., Ang, K. Y., Huang, S., Hou, Q., Su, X., Qiao, J., Zheng, Y., Wang, L., et al. (2016) · Scientific Reports · doi:10.1038/srep20602 · Cited by 382
Wang, J., Chen, Y., Zhong, H., Chen, F., Regenstein, J., Hu, X., Cai, L., & Feng, F. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1874287 · Cited by 317
Trifirò, G., Morabito, P., Cavagna, L., Ferrajolo, C., Pecchioli, S., Simonetti, M., Bianchini, E., Medea, G., Cricelli, C., Caputi, A. P., et al. (2013) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2011-201254 · Cited by 272
Metadata
- Authors
- Hosomi, A., Nakanishi, T., Fujita, T., & Tamai, I.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-02-10
- Volume
- 7
- Issue
- 2
- Pages
- e30456
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2071730213
- Cited by
- 258
- References
- 2
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- gold
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- Hosomi, A., Nakanishi, T., Fujita, T., & Tamai, I. (2012). Extra-Renal Elimination of Uric Acid via Intestinal Efflux Transporter BCRP/ABCG2. PLoS ONE. https://doi.org/10.1371/journal.pone.0030456
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