Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital , Memphis, TN, USA.
Graduate School of Biomedical Sciences, St. Jude Children's Research Hospital , Memphis, TN, USA.
Expert Opin Drug Metab Toxicol. 2020 Aug;16(8):711-722. doi: 10.1080/17425255.2020.1779701. Epub 2020 Jun 16.
The human liver is the center for drug metabolism and detoxification and is, therefore, constantly exposed to toxic chemicals. The loss of liver function as a result of this exposure is referred to as drug-induced liver injury (DILI). The pregnane X receptor (PXR) is the primary regulator of the hepatic drug-clearance system, which plays a critical role in mediating idiosyncratic DILI.
This review is focused on common mechanisms of PXR-mediated DILI and on and models developed to predict and assess DILI. It also provides an update on the development of PXR antagonists that may manage PXR-mediated DILI.
DILI can be caused by many factors, and PXR is clearly linked to DILI. Although emerging data illustrate how PXR mediates DILI and how PXR activity can be modulated, many questions concerning the development of effective PXR modulators remain. Future research should be focused on determining the mechanisms regulating PXR functions in different cellular contexts.
人类肝脏是药物代谢和解毒的中心，因此经常接触有毒化学物质。由于这种接触而导致的肝功能丧失被称为药物性肝损伤（DILI）。孕烷 X 受体（PXR）是调节肝脏药物清除系统的主要调节剂，在介导特发性 DILI 中起着关键作用。
本综述重点介绍了 PXR 介导的 DILI 的常见机制，以及用于预测和评估 DILI 的 和 模型。它还提供了关于开发可能管理 PXR 介导的 DILI 的 PXR 拮抗剂的最新信息。
DILI 可能由多种因素引起，而 PXR 显然与 DILI 有关。尽管新出现的数据说明了 PXR 如何介导 DILI 以及如何调节 PXR 活性，但关于开发有效的 PXR 调节剂仍存在许多问题。未来的研究应集中于确定调节不同细胞环境中 PXR 功能的机制。
