Involvement of metabolic enzymes and transporters in diclofenac-induced liver injury

代谢酶和转运蛋白参与双氯芬酸诱导的肝损伤

• 批准号: 23590210
• 负责人: IWAKI Masahiro
• 金额: $ 3.33万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590210/
• 关键词: 薬物動態・代謝学; 肝毒性; トランスポーター; 代謝酵素; 反応性代謝物; siRNA; アシルグルクロナイド

We examined the involvement of CYP2C9, UGT2B7, MRP2 and MRP3 in induction of diclofenac (DF)-induced hepatotoxicity. In primary cultured rat hepatocytes, the knockdown for MRP2 resulted in the accumulation of DF-Glu to cells. Whereas, the knockdown for MRP3 exhibited little alterations in the accumulation of DF-Glu to cells. The higher hepatotoxicity was observed in MRP2 knockdown cells compared with MRP3 knockdown cells, suggesting that MRP2 is more important in induction of hepatotoxicity by DF.

我们检测了CYP2C9、UGT2B7、MRP2和MRP3在双氯芬酸（DF）诱导的肝毒性诱导中的作用。在原代培养的大鼠肝细胞中，MRP2的敲低导致DF-Glu向细胞积聚。然而，MRP3的敲除对细胞中DF-Glu的积累几乎没有改变。与MRP3敲低细胞相比，MRP2敲低细胞的肝毒性更高，表明MRP2在DF诱导肝毒性中更重要。