Evaluation of the intestinal secretion of indoxyl sulfate as a possible compensative excretion pathway in chronic kidney disease
| Project/Area Number |
25460196
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tohoku Pharmaceutical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TOMITA Mikio 東北薬科大学, 薬学部, 教授 (60207610)
OGIHARA Takuo 高崎健康福祉大学, 薬学部, 教授 (80448886)
YANO Kentaro 高崎健康福祉大学, 薬学部, 助手 (40644290)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | トランスポーター / 消化管 / 腎不全 / 尿毒症 / インドキシル硫酸 / 消化管分泌 / 小腸 / Indoxyl Sulfate / ABC transporter |
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| Outline of Final Research Achievements |
During chronic kidney disease (CKD), protein-bound uremic toxins such as indoxyl sulfate (IS) cannot be efficiently removed by hemodialysis. Progressive accumulation of IS is an important risk factor in the progression of CKD and cardiovascular disease. Previous report suggested that non-renal clearance was observed in CKD rat, in spite of the significant renal excretion in healthy condition. Therefore, we focused on the possibility of the involvement of intestinal secretion as an alternative excretion pathway of IS in CKD. We found that IS was secreted into jejunum lumen in normal and CKD rats. The contribution of the gut secretion to the total clearance was very low but increased dependent dosage. For cell-based assay, Na+-dependent vectorial transport of IS across a Caco-2 cell monolayer was observed, with higher transport in the basolateral-to-apical direction. These results suggest that IS is actively secreted into the gut predominantly via Na+-dependent efflux transporters.
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Report
(4 results)
Research Products
(7 results)
