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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
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PXR-mediated idiosyncratic drug-induced liver injury: mechanistic insights and targeting approaches

Jingheng Wang1, Monicah Bwayi1, Rebecca R Florke Gee1,2

  • 1Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital , Memphis, TN, USA.

Expert Opinion on Drug Metabolism & Toxicology
|June 6, 2020
PubMed
Abstract

Insights

Drug-induced liver injury (DILI) is linked to the pregnane X receptor (PXR). This review covers PXR-mediated DILI mechanisms, models, and potential PXR antagonist therapies.

Area of Science:

  • Hepatology
  • Pharmacology
  • Toxicology

Background:

  • The liver metabolizes drugs and is exposed to toxins, leading to drug-induced liver injury (DILI).
  • The pregnane X receptor (PXR) regulates hepatic drug clearance and is implicated in idiosyncratic DILI.

Purpose of the Study:

  • To review PXR-mediated DILI mechanisms.
  • To discuss in vitro and in vivo models for DILI assessment.
  • To update on PXR antagonist development for DILI management.

Main Methods:

  • Literature review of PXR-mediated DILI.
  • Analysis of in vitro and in vivo DILI models.
  • Review of PXR antagonist research.

Main Results:

  • PXR is a key mediator of DILI.
  • Various models exist to study DILI.
  • PXR antagonists are under development for DILI treatment.

Conclusions:

  • PXR plays a significant role in DILI.
  • Understanding PXR's role is crucial for DILI management.
  • Further research is needed on PXR regulation in different cellular contexts.
Keywords:
Adverse drug reactiondrug metabolismdrug-induced liver injuryliver toxicitypregnane X receptor

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