Elucidation of the mechanism of human-specific drug hepatotoxicity using a novel humanized liver mouse model of drug-induced liver injury

利用新型人源化肝小鼠药物性肝损伤模型阐明人类特异性药物肝毒性机制

• 批准号: 20K06463
• 负责人: Uehara Shotaro
• 金额: $ 2.75万
• 依托单位: Central Institute for Experimental Animals
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20K06463/
• 关键词: ヒト化肝臓マウス; チトクロムP450; チトクロムP450酸化還元酵素; TK-NOGマウス; 薬物代謝; S-ワルファリン; 肝臓特異的Por欠損; 薬物代謝の動物種差; POR; ヒト型薬物代謝; ヒト肝キメラマウス; ワルファリン代謝; 肝毒性; 代謝的活性化

项目成果

Roles of human cytochrome P450 1A2 in coumarin 3,4-epoxidation mediated by untreated hepatocytes and by those metabolically inactivated with furafylline in previously transplanted chimeric mice

人细胞色素 P450 1A2 在香豆素 3,4-环氧化中的作用，该作用由未经处理的肝细胞和先前移植的嵌合小鼠中用呋拉茶碱代谢灭活的肝细胞介导

• DOI: 10.2131/jts.46.525
• 发表时间: 2021
• 期刊: The Journal of Toxicological Sciences
• 作者: Miura Tomonori;Uehara Shotaro;Shimizu Makiko;Murayama Norie;Suemizu Hiroshi;Yamazaki Hiroshi
• 通讯作者: Yamazaki Hiroshi

In vivo drug interactions of itopride and trimethylamine mediated by flavin-containing monooxygenase 3 in humanized-liver mice

含黄素单加氧酶 3 介导的伊托必利和三甲胺在人源化肝小鼠体内的药物相互作用

• DOI: 10.1016/j.dmpk.2020.11.004
• 发表时间: 2021
• 期刊: Drug Metabolism and Pharmacokinetics
• 影响因子: 2.1
• 作者: Shimizu Makiko;Uehara Shotaro;Suemizu Hiroshi;Yamazaki Hiroshi
• 通讯作者: Yamazaki Hiroshi

Expression and functional activity of cytochrome P450 enzymes in human hepatocytes with sustainable reproducibility for in vitro phenotyping studies.

人肝细胞中细胞色素 P450 酶的表达和功能活性，在体外表型研究中具有可持续的重现性。

• DOI: 10.1016/bs.apha.2022.05.009
• 发表时间: 2022
• 期刊: Adv Pharmacol.
• 作者: Bachour-El Azzi P;Chesne C;Uehara S.
• 通讯作者: Uehara S.

Human Aldehyde Oxidase 1-Mediated Carbazeran Oxidation in Chimeric TK-NOG Mice Transplanted with Human Hepatocytes.

人醛氧化酶 1 介导的嵌合 TK-NOG 小鼠移植人肝细胞后的卡巴泽兰氧化。

• DOI: 10.1124/dmd.120.091090
• 发表时间: 2020
• 期刊: Drug Metab Dispos.
• 作者: Uehara S;Yoneda N;Higuchi Y;Yamazaki H;Suemizu H.
• 通讯作者: Suemizu H.

Hepatotoxicological potential of P-toluic acid in humanised-liver mice investigated using simplified physiologically based pharmacokinetic models

使用简化的基于生理学的药代动力学模型研究对甲基苯甲酸在人源化肝小鼠中的肝毒理学潜力

• DOI: 10.1080/00498254.2021.1908643
• 发表时间: 2021
• 期刊: Xenobiotica
• 影响因子: 1.8
• 作者: Miura Tomonori;Kamiya Yusuke;Uehara Shotaro;Murayama Norie;Shimizu Makiko;Suemizu Hiroshi;Yamazaki Hiroshi
• 通讯作者: Yamazaki Hiroshi