PXR-mediated idiosyncratic drug-induced liver injury: mechanistic insights and targeting approaches
Jingheng Wang, Monicah N Bwayi, Rebecca R. Florke Gee, Taosheng Chen
Abstract
INTRODUCTION: 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. AREAS COVERED: models developed to predict and assess DILI. It also provides an update on the development of PXR antagonists that may manage PXR-mediated DILI. EXPERT OPINION: 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.