Developments in estimation of the functional changes of transporters and drug metabolizing enzymes during renal failure
| Project/Area Number |
16K18934
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
Masuo Yusuke 金沢大学, 薬学系, 助教 (90708140)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | トランスポーター / 慢性腎障害 / 尿毒素 / メタボロミクス / 膜輸送体 / メタボローム解析 / 薬物動態 / ヒトの薬物動態 / 肝膜輸送体 / 薬物代謝酵素 |
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| Outline of Final Research Achievements |
Several uremic tocxins have been proposed to inhibit hepatic uptake transporters. The purpose of this study is to find possible inhibition of OATP1B1 by newly identified uremic toxins, 6-OH indole. 6-OH indole inhibited OATP1B1-mediated uptake of [3H]estrone sulfate in HEK293/OATP1B1 cells. Plasma concentration of 6-OH indole was higher in patients with severe renal failure than that in patients without renal failure. The inhibition pattern of OATP1B1 by 6-OH indole was long-lasting, since its inhibition was maintained after 6-OH indole was washed out. Also, 6-OH indole inhibited uptake of estrone sulfate in primary cultured hepatocytes without changing mRNA expression of OATP1B1. These results suggest that increase of 6-OH indole in plasma during CKD could at least partially explain the delayed elimination of OATP1B1 substrate drugs.
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Report
(3 results)
Research Products
(34 results)
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[Journal Article] Farnesoid X Receptor Protects Against Low-Dose Carbon Tetrachloride-Induced Liver Injury Through the Taurocholate-JNK Pathway.2017
Author(s)
Takahashi S, Tanaka N, Golla S, Fukami T, Krausz KW, Polunas MA, Weig BC, Masuo Y, Xie C, Jiang C, Gonzalez FJ.
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Journal Title
Toxicol Sci.
Volume: 158
Issue: 2
Pages: 334-346
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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