Electrochemical analysis of uric acid excretion to the intestinal lumen: Effect of serum uric acid-lowering drugs and 5/6 nephrectomy on intestinal uric acid levels


Autoři: Kyoko Fujita aff001;  Hiroki Yamada aff001;  Masahiro Iijima aff001;  Kimiyoshi Ichida aff001
Působiště autorů: Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Horinouchi, Hachioji, Tokyo, Japan aff001
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226918

Souhrn

Recently, extensive efforts have been made to understand the importance of the extra-renal uric acid (UA) excretion pathways and their contribution to UA-related diseases. However, the method typically used to measure UA concentrations in the intestinal lumen is difficult to real time and dynamic analysis. In this study, UA excretion in the rat intestinal lumen was measured in real time using an electrochemical method. A sensitive electrode to detect UA was constructed using a gold electrode modified with a mixed self-assembled monolayer. Excretion rate of UA in the intestine was calculated using time course data. A decrease in UA excretion rate was observed in the intestine after administration of serum UA-lowering drugs (benzbromarone, febuxostat, and topiroxostat). Inhibition of ATP-binding cassette transporter G2 (ABCG2) which has been reported as an important exporter of UA was suggested by administration of these drugs. On the other hand, an increase in excretion rate of UA was observed in the intestine of 5/6 nephrectomy rats. Upregulation of mRNA expression of the UA transporter organic anion transporter OAT3, which is related to the secretion at the basal membrane, suggested an enhancement of UA excretion by ABCG2, a high-capacity UA exporter. Observed urate excretion dynamics and mRNA expression of UA transporters in the intestine upon administration of serum UA-lowering drugs and 5/6 nephrectomy improve our understanding of the underlying mechanisms of intestinal UA excretion.

Klíčová slova:

Drug administration – Drug therapy – Electrochemistry – Excretion – Gastrointestinal tract – Gene expression – Ileum – Nephrectomy


Zdroje

1. Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. The New England journal of medicine. 2008;359:1811–21. doi: 10.1056/NEJMra0800885 18946066

2. Kawashima M, Wada K, Ohta H, Terawaki H, Aizawa Y. Association between asymptomatic hyperuricemia and new-onset chronic kidney disease in Japanese male workers: a long-term retrospective cohort study. BMC nephrology. 2011;12:31. doi: 10.1186/1471-2369-12-31 21722384.

3. Odden MC, Amadu A-R, Smit E, Lo L, Peralta CA. Uric acid levels, kidney function, and cardiovascular mortality in US adults: National Health and Nutrition Examination Survey (NHANES) 1988–1994 and 1999–2002. American journal of kidney diseases: the official journal of the National Kidney Foundation. 2014;64:550–7. doi: 10.1053/j.ajkd.2014.04.024 24906981.

4. Zhong LL, Song YQ, Tian XY, Cao H, Ju KJ. Level of uric acid and uric acid/creatinine ratios in correlation with stage of Parkinson disease. Medicine. 2018;97(26):e10967. Epub 2018/06/29. doi: 10.1097/MD.0000000000010967 29952939; PubMed Central PMCID: PMC6039589.

5. Paganoni S, Schwarzschild MA. Urate as a Marker of Risk and Progression of Neurodegenerative Disease. Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics. 2017;14(1):148–53. Epub 2016/12/21. doi: 10.1007/s13311-016-0497-4 27995438; PubMed Central PMCID: PMC5233635.

6. Anzai N, Kanai Y, Endou H. New insights into renal transport of urate. Current opinion in rheumatology. 2007;19(2):151–7. Epub 2007/02/07. doi: 10.1097/BOR.0b013e328032781a 17278930.

7. Endou H, Anzai N. Urate transport across the apical membrane of renal proximal tubules. Nucleosides, nucleotides & nucleic acids. 2008;27(6):578–84. Epub 2008/07/05. doi: 10.1080/15257770802136024 18600508.

8. Preitner F, Bonny O, Laverriere A, Rotman S, Firsov D, Da Costa A, et al. Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(36):15501–6. Epub 2009/08/27. doi: 10.1073/pnas.0904411106 19706426; PubMed Central PMCID: PMC2741280.

9. Woodward OM, Kottgen A, Coresh J, Boerwinkle E, Guggino WB, Kottgen M. Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:10338–42. doi: 10.1073/pnas.0901249106 19506252

10. Matsuo H, Takada T, Ichida K, Nakamura T, Nakayama A, Ikebuchi Y, et al. Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population. Science Translational Medicine. 2009;1:5ra11. doi: 10.1126/scitranslmed.3000237 20368174

11. Matsuo H, Nakayama A, Sakiyama M, Chiba T, Shimizu S, Kawamura Y, et al. ABCG2 dysfunction causes hyperuricemia due to both renal urate underexcretion and renal urate overload. Scientific reports. 2014;4:3755. doi: 10.1038/srep03755 24441388.

12. Sorensen LB. Role of the intestinal tract in the elimination of uric acid. Arthritis and rheumatism. 1965;8(5):694–706. Epub 1965/10/01. doi: 10.1002/art.1780080429 5859543.

13. Vaziri ND, Freel RW, Hatch M. Effect of chronic experimental renal insufficiency on urate metabolism. Journal of the American Society of Nephrology: JASN. 1995;6(4):1313–7. Epub 1995/10/01. 8589304.

14. Yano H, Tamura Y, Kobayashi K, Tanemoto M, Uchida S. Uric acid transporter ABCG2 is increased in the intestine of the 5/6 nephrectomy rat model of chronic kidney disease. Clinical and experimental nephrology. 2014;18(1):50–5. Epub 2013/04/16. doi: 10.1007/s10157-013-0806-8 23584883.

15. Ichida K, Matsuo H, Takada T, Nakayama A, Murakami K, Shimizu T, et al. Decreased extra-renal urate excretion is a common cause of hyperuricemia. Nature Communications. 2012;3:764–70. doi: 10.1038/ncomms1756 22473008.

16. Miyata H, Takada T, Toyoda Y, Matsuo H, Ichida K, Suzuki H. Identification of Febuxostat as a New Strong ABCG2 Inhibitor: Potential Applications and Risks in Clinical Situations. Frontiers in pharmacology. 2016;7:518. Epub 2017/01/14. doi: 10.3389/fphar.2016.00518 28082903; PubMed Central PMCID: PMC5187494.

17. Ganeval D, Marche C, Drueke T. Perfusion of an isolated jejunal loop in uremic rats: Effect of sodium deoxycholate. Kidney international. 1973;3(4):222–9. Epub 1973/04/01. doi: 10.1038/ki.1973.35 4792038.

18. Fujita K, Nakamura N, Ohno H, Leigh BS, Niki K, Gray HB, et al. Mimicking protein-protein electron transfer: Voltammetry of Pseudomonas aeruginosa azurin and the Thermus thermophilus Cu-A domain at omega-derivatized self-assembled-monolayer gold electrodes. Journal of the American Chemical Society. 2004;126(43):13954–61. doi: 10.1021/ja047875o WOS:000224873600036. 15506756

19. Tan PK, Miner JN. Uric acid transporter inhibitors for gout. ADMET & DMPK. 2017;5(2):59–74. doi: 10.5599/admet.5.2.387

20. Ichida K, Hosoyamada M, Kimura H, Takeda M, Utsunomiya Y, Hosoya T, et al. Urate transport via human PAH transporter hOAT1 and its gene structure. Kidney international. 2003;63(1):143–55. Epub 2002/12/11. doi: 10.1046/j.1523-1755.2003.00710.x 12472777.

21. Eraly SA, Vallon V, Rieg T, Gangoiti JA, Wikoff WR, Siuzdak G, et al. Multiple organic anion transporters contribute to net renal excretion of uric acid. Physiological genomics. 2008;33(2):180–92. Epub 2008/02/14. doi: 10.1152/physiolgenomics.00207.2007 18270321; PubMed Central PMCID: PMC3016923.

22. Xu L, Shi Y, Zhuang S, Liu N. Recent advances on uric acid transporters. Oncotarget. 2017;8(59):100852–62. Epub 2017/12/17. doi: 10.18632/oncotarget.20135 29246027; PubMed Central PMCID: PMC5725069.

23. Akazawa T, Uchida Y, Tachikawa M, Ohtsuki S, Terasaki T. Quantitative Targeted Absolute Proteomics of Transporters and Pharmacoproteomics-Based Reconstruction of P-Glycoprotein Function in Mouse Small Intestine. Molecular pharmaceutics. 2016;13(7):2443–56. Epub 2016/06/09. doi: 10.1021/acs.molpharmaceut.6b00196 27276518.

24. Van Aubel RA, Smeets PH, van den Heuvel JJ, Russel FG. Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites. American journal of physiology Renal physiology. 2005;288(2):F327–33. Epub 2004/09/30. doi: 10.1152/ajprenal.00133.2004 15454390.

25. Taylor NMI, Manolaridis I, Jackson SM, Kowal J, Stahlberg H, Locher KP. Structure of the human multidrug transporter ABCG2. Nature. 2017;546(7659):504–9. Epub 2017/05/30. doi: 10.1038/nature22345 28554189.

26. Wu W, Bush KT, Nigam SK. Key Role for the Organic Anion Transporters, OAT1 and OAT3, in the in vivo Handling of Uremic Toxins and Solutes. Scientific reports. 2017;7(1):4939. Epub 2017/07/12. doi: 10.1038/s41598-017-04949-2 28694431; PubMed Central PMCID: PMC5504054.

27. Russel FG, Koenderink JB, Masereeuw R. Multidrug resistance protein 4 (MRP4/ABCC4): a versatile efflux transporter for drugs and signalling molecules. Trends in pharmacological sciences. 2008;29(4):200–7. Epub 2008/03/21. doi: 10.1016/j.tips.2008.01.006 18353444.

28. Liu HC, Goldenberg A, Chen Y, Lun C, Wu W, Bush KT, et al. Molecular Properties of Drugs Interacting with SLC22 Transporters OAT1, OAT3, OCT1, and OCT2: A Machine-Learning Approach. The Journal of pharmacology and experimental therapeutics. 2016;359(1):215–29. Epub 2016/08/05. doi: 10.1124/jpet.116.232660 27488918; PubMed Central PMCID: PMC5034704.

29. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, et al. Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Molecular pharmacology. 2001;59(5):1277–86. Epub 2001/04/18. doi: 10.1124/mol.59.5.1277 11306713.


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