MicroRNAs as biomarkers for drug-induced liver injury

MicroRNA 作为药物性肝损伤的生物标志物

• 批准号: 21390174
• 负责人: YOKOI Tsuyoshi
• 金额: $ 12.4万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390174/
• 关键词: 薬物誘導性肝障害; マイクロRNA; チトクロムP450; 転写因子; microRNA; ハロタン; 肝細胞障害モデル動物; ヒト肝障害患者血清; バイオマーカー; 末梢血microRNA; ターゲットタンパク質; ヘルパーT細胞; 肝細胞障害モデルラット; 胆汁うっ滞モデルラット

Because of the significant adverse drug reactions associated with hepatotoxicity, several drugs have been removed from the pharmaceutical market. In most cases, the mechanisms of the hepatotoxicity are unknown and predictive experimental animal models are lacking. Thus, experimental animal models of drug-induced liver injury will enable to perform comprehensive analyses for predictive toxicity studies. The miRNA research in the metabolism of xenobiotics and endobiotics and in toxicology has only recently been established. We performed studies with the following titles,(1) Establishment of halothane-induced liver injury in mice and involvement of miRNA on early onset of liver injury.(2) Involvement of immune-related factors and miRNA in the mouse model of diclofenac-induced liver injury.(3) Establishment of the mouse model of flucloxacillin-induced liver injury.(4) Plasma microRNA profiles in rat models of hepatocellular injury, cholestasis, and steatosis.(5) Peroxisome proliferator-activator receptor. is regulated by miR-21 and miR-27b in human liver

由于与肝毒性相关的严重不良反应，几种药物已被从药品市场上撤下。在大多数情况下，肝毒性的机制尚不清楚，也缺乏预测性的实验动物模型。因此，药物性肝损伤的实验动物模型将能够为预测性毒性研究进行全面的分析。MiRNA在外源和内源物质的代谢以及毒理学方面的研究只是最近才建立起来的。我们开展了以下研究：(1)氟烷诱导的小鼠肝损伤模型的建立及miRNA在早期肝损伤中的作用；(2)免疫相关因子和miRNA在双氯芬酸诱导的小鼠肝损伤模型中的作用；(3)氟氯西林诱导的小鼠肝损伤模型的建立；(4)大鼠肝细胞损伤、胆汁淤积和脂肪变性模型中血浆microRNA的变化。(5)过氧酶体增殖物-激活剂受体。在人肝脏中受miR-21和miR-27b调控

项目成果

研究室のwwwsite:

实验室网址：

CYP2C9-mediated metabolic activation of losartan detected by a highly sensitive cell-cased screening assay

通过高度灵敏的细胞筛选试验检测 CYP2C9 介导的氯沙坦代谢激活

• DOI: 10.1124/dmd.110.037259
• 发表时间: 2011
• 期刊: Drug Metabolism and Disposition
• 影响因子: 3.9
• 作者: Atsushi Iwamura;et al
• 通讯作者: et al

Human Paraoxonase 1 Is the Enzyme Responsible for Pilocarpine Hydrolysis

• DOI: 10.1124/dmd.111.038141
• 发表时间: 2011-08-01
• 期刊: DRUG METABOLISM AND DISPOSITION
• 影响因子: 3.9
• 作者: Hioki, Tomomi;Fukami, Tatsuki;Yokoi, Tsuyoshi
• 通讯作者: Yokoi, Tsuyoshi

Establishment of knockdown of superoxide dismutase 2 and expression of CYP3A4 cell system to evaluate drug-induced cytotoxicity

• DOI: 10.1016/j.tiv.2009.05.024
• 发表时间: 2009-09-01
• 期刊: TOXICOLOGY IN VITRO
• 影响因子: 3.2
• 作者: Yoshikawa, Yukitaka;Hosomi, Hiroko;Yokoi, Tsuyoshi
• 通讯作者: Yokoi, Tsuyoshi

薬物代謝に関与する酵素とその反応機構,薬物代謝と毒性発現「薬物代謝学医療薬学・医薬品開発の基礎として第3版」

参与药物代谢的酶及其反应机制、药物代谢和毒性表达《药物代谢作为医学药剂学和药物开发基础，第3版》

• 发表时间: 2010
• 作者: Kugimiya T;Jono H;Saito S;Maruyama T;Kadowaki D;Misumi Y;Hoshii Y;Tasaki M;Su Y;Ueda M;Obayashi K;Shono M;Otagiri M;Ando Y;横井毅
• 通讯作者: 横井毅