2021 Fiscal Year Final Research Report
Study of Effects of Nanocarbon on the Expression and Activities of Drug-Metabolizing Enzymes and Drug Transporters for Safety Assessment
Project/Area Number |
19K07233
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | Meijo University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
加藤 美紀 名城大学, 薬学部, 准教授 (70345594)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | ナノ炭素材料 / 単層カーボンナノチューブ / 第Ⅰ相薬物代謝酵素 / 第Ⅱ相薬物代謝酵素 / 薬物トランスポーター / 肝臓 / 消化管 |
Outline of Final Research Achievements |
Recently, clinical application of nanocarbon, including single-walled carbon nanotube (SWCNTs), has been proposed as drug delivery agents. However, there is a growing concern about the toxicity of SWCNTs on the biological systems. The present study aimed to elucidate the effect of nanocarbon, especially SWCNTs, on the expression and activities of phase I and phase II drug-metabolizing enzymes in the human and rat liver in vitro. In addition, the effects of nanocarbon on the expression of drug transporters in Caco-2 cell and Cellartis Intestinal Epithelial Cells, which are small intestinal epithelial cells derived from human iPS cells, were examined. Results of this study suggested that SWCNTs affect the expression and activities of drug-metabolizing enzymes and drug transporters. The effects of SWCNTs were different among isoforms of the enzymes or transporters, and that the effect may be dependent on the physicochemical properties of SWCNT.
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Free Research Field |
薬物動態学
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Academic Significance and Societal Importance of the Research Achievements |
カーボンナノチューブ等のナノ炭素材料は、医療材料としての需要拡大と同時に、その生体に対する安全性の評価が求められている。 生体の主要な異物処理臓器である肝臓や腎臓では、薬物代謝酵素やトランスポーターの発現が高いが、ナノ炭素材料がこれら臓器及び細胞の生理状態や異物処理機能に影響を及ぼす可能性がある。したがって、ナノ炭素材料を生体主要臓器(細胞)に暴露した際の生理学的・生化学的変化について、生体の異物処理機構である薬物代謝酵素やトランスポーターに及ぼす影響を中心に、毒性学、薬物動態学的観点から検討することは、ナノ炭素材料の工学材料、医療材料としての安全性と有用性の評価に不可欠である。
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