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

我们研究了CYP2C9、UGT2B7、MRP2和MRP3在双氯芬酸(DF)诱导的肝毒性中的作用。在原代培养的大鼠肝细胞中，MRP2基因敲除导致DF-Glu积聚到细胞内。然而，MRP3基因被敲除后，细胞内DF-Glu的积聚几乎没有变化。与MRP3基因敲除细胞相比，MRP2基因敲除细胞具有更高的肝毒性，提示MRP2在DF诱导肝毒性中起更重要的作用。

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.