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Utility of human hepatocyte spheroids without feeder cells for evaluation of hepatotoxicity
https://doi.org/10.24517/00015210
https://doi.org/10.24517/00015210cb8205b1-d278-40b3-b192-efaa68be5008
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
PH-PR-ARAKAWA-H-499.pdf (2.1 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||||
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| 公開日 | 2018-06-14 | |||||||
| タイトル | ||||||||
| タイトル | Utility of human hepatocyte spheroids without feeder cells for evaluation of hepatotoxicity | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||
| 資源タイプ | journal article | |||||||
| ID登録 | ||||||||
| ID登録 | 10.24517/00015210 | |||||||
| ID登録タイプ | JaLC | |||||||
| 著者 |
Ogihara, Takuo
× Ogihara, Takuo× Arakawa, Hiroshi× Jomura, Tomoko× Idota, Yoko× Koyama, Satoshi× Yano, Kentaro× Kojima, Hajime |
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| 著者別表示 |
荒川, 大
× 荒川, 大
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| 書誌情報 |
The Journal of Toxicological Sciences 巻 42, 号 4, p. 499-507, 発行日 2017-08-01 |
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| ISSN | ||||||||
| 収録物識別子タイプ | ISSN | |||||||
| 収録物識別子 | 0388-1350 | |||||||
| NCID | ||||||||
| 収録物識別子タイプ | NCID | |||||||
| 収録物識別子 | AA11508363 | |||||||
| DOI | ||||||||
| 関連タイプ | isIdenticalTo | |||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | 10.2131/jts.42.499 | |||||||
| 出版者 | ||||||||
| 出版者 | The Japanese Society of Toxicology = 日本毒性学会 | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | We investigated the utility of three-dimensionally cultured hepatocytes (spheroids) without feeder cells (Sph(f-)) for the prediction of drug-induced liver injury (DILI) in humans. Sph(f-) and spheroids cultured on feeder cells (Sph(f+)) were exposed to the hepatotoxic drugs flutamide, diclofenac, isoniazid and chlorpromazine at various concentrations for 14 days, and albumin secretion and cumulative leakages of toxicity marker enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GTP), were measured. The cumulative AST, LDH or γ-GTP leakages from Sph(f-) were similar to or greater than those from Sph(f+) for all drugs tested, although ALT leakages showed no consistent difference between Sph(f+) and Sph(f-). In the case of Sph(f-), significant correlations among all the toxicity markers except for γ-GTP were observed. As regards the drug concentrations causing 1.2-fold elevation of enzyme leakage (F1.2), no consistent difference between Sph(f+) and Sph(f-) was found, although several F1.2 values were undetermined, especially in Sph(f+). The IC50 of albumin secretion and F1.2 of AST leakage from Sph(f-) were equal to or lower than those of Sph(f+) for all the tested drugs. These results indicate that feeder cells might contribute to resistance to hepatotoxicity, suggesting DILI could be evaluated more accurately by using Sph(f-). We suggest that long-term exposure of Sph(f-) to drugs might be a versatile method to predict and reproduce clinical chronic toxicity, especially in response to repeated drug administration. | |||||||
| 権利 | ||||||||
| 権利情報 | Copyright © 2017 The Japanese Society of Toxicology 日本毒性学会 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
| 関連URI | ||||||||
| 識別子タイプ | URI | |||||||
| 関連識別子 | http://www.jsot.jp/ | |||||||
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| 識別子タイプ | URI | |||||||
| 関連識別子 | https://www.jstage.jst.go.jp/browse/jts | |||||||
