| Project/Area Number |
12470509
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
SUZUKI Kazuo CHIBA UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, PROFESSOR, 大学院・薬学研究院, 教授 (90109918)
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| Co-Investigator(Kenkyū-buntansha) |
OGRA Yasumitsu GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, RESEARCH ASSOCIATE, 大学院・薬学研究院, 助手 (40292677)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2001: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | SELENIUM / SPECIATION / ICP-MS / STABLE ISOTOPE / SELENOAMINO ACIDS / SELENOSUGAR / ESI-MS / MS / NUTRIENT / HPLC / セレノプロテインP / ヒ素 |
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| Research Abstract |
Mechanisms underlying the metabolic transformation of the micronutrient selenium in the body have been studied based on the speciation technique.
1. Selenium chemicals labeled with an enriched stable isotope were administered to rats, and the chemical forms of the labeled selenium were determined by the HPLC-ICP MS method with simultaneous detection of multi-elements.
2. Both organic and inorganic forms of selenium can be utilized as the nutritional source for selenium. Inorganic forms of selenium, selenite and selenate labeled with an enriched selenium were administered intravenously or orally to rats, and the chemical forms of labeled selenium in the bloodstream, liver and urine were determined by the HPLC-ICP MS method. The major urinary selenium metabolite was obtained by feeding adequate (0.2 μg/g diet) and excessive selenium (2.0 μg/g diet). The chemical structure was deduced to be a new selenium-containing sugar (selenosugar) by mass spectrometric and ^1H-NMR data.
3. The metabolic
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pathways for organic forms of selenium were studied using a representative selenoamino acid, selenomethionine. ^<82>Se-Enriched selenomethionine was synthesized chemically, and it was administered to rats. Selenium of selenomethionine was excreted into the urine in the form of the same selenosugar as that of inorganic selenite, suggesting selenium of selenomethionine is metabolized with recognition of selenomethionine as selenium even by feeding it at an excessive dose.
4. Efficiency for the utilization of selenium was compared between inorganic selenite and organic selenomethionine by feeding enriched ones at adequate and excessive doses. The relative ratios between enriched and naturally occurring selenium were determined for most of organs and body fluids with time after feeding them for 30 days. Characteristics in the exchange ratios were pointed out among organs and between the two nutritional selenium chemicals.
5. Biological interactions of selenium with other elements were focused on the formation of ternary complex between mercury, selenium and the plasma protein selenoprotein P previuously and now on arsenic. Precise metabolic pathway for arsenic in the liver was revealed based on the speciation data after administering arsenite to rats, especially by characterizing chemical forms of arsenic in the bile, namely metabolites by methylation and reduction reactions, and conjugation with glutathione. Less
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