Analysis of the mechanisms of absorption and elimination of chemical products in cultured cells and its application for estimation of the toxicity in vivo
| Project/Area Number |
12680552
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | Josai University |
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Principal Investigator |
KUDO Naomi Josai University, Faculty of Pharmaceutical Sciences, Lecturer, 薬学部, 講師 (10161647)
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| Co-Investigator(Kenkyū-buntansha) |
藤兼 裕子 城西大学, 薬学部, 研究助手
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | perfluooctanoic acid / renal clearance / organic anion transporter / sex hormone / intestinal absorption / フッ素化脂肪酸 / 腎排泄 |
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| Research Abstract |
In this study, mechanism of the transport of perfluorooctanoic acid (PFOA) in biological system was investigated in vivo and in vitro. PFOA was efficiently absorbed after an oral administration. Transport studies using everted sacs and brush border membranes of small intestine of rats revealed that some transporters are responsible for intestinal absorption of PFOA.
There was a significant sex-related difference in renal clearance of PFOA. Comparison of renal clearance of PFOA with mRNA expression of various organic anion transporters in rat with various hormonal states suggested that OAT2, OAT3 and oatp 1 were responsible for renal transport of PFOA. OAT3 protein expressed in brush border membrane of renal tubules and the expression was regulated by estradiol but not by testosterone.
Overexpression of both oatp 1 and OAT3 significantly increased PFOA uptake while OAT2 did not in Xenopus oocytes.
The above results suggest that PFOA is taken up from blood via OAT3 and excreted into urine and that oatp 1 is responsible for re-absorption of PFOA. The results are useful to establish the in vitro system to estimate toxicokinetics of various chemical products.
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Report
(4 results)
Research Products
(15 results)
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[Publications] Kudo, N., Suzuki, E., Katakura, M., Ohmori, K., Noshiro, R. and Kawashima, Y.: "Comparison of the elimination between perfluorinated fatty acids with different carbon chain length in rats"Chemico-Biol. Interact.. 134. 203-216 (2001)
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[Publications] Katakura, M., Kudo, N., N., Okazaki, M., Hibino, Y. and Kawashima, Y.: "Sex hormone regulation of rOAT3 expression in rat kidney"J. Health Sci., in press.
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