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Cell-based approaches for the mechanistic understanding of drug-induced cholestatic liver injury

Enrique Timor-López1,2, Laia Tolosa3,4, M Teresa Donato5,6,7

  • 1Experimental Hepatology Unit, Health Research Institute La Fe (IISLAFE), Torre A. Instituto Investigación Sanitaria La Fe Av Fernando Abril Martorell 106, 46026, Valencia, Spain.

Archives of Toxicology
|March 11, 2025
PubMed

Insights

Drug-induced cholestasis, a liver injury from medications, causes significant health issues. This review covers its mechanisms and current in vitro models for predicting drug cholestatic potential.

Area of Science:

  • Hepatology
  • Toxicology
  • Drug Development

Background:

  • Drug-induced cholestasis is a major cause of drug-induced liver injury (DILI).
  • It significantly impacts patient health, healthcare costs, and drug development.
  • Key features include impaired bile acid homeostasis, hepatocellular injury, and canalicular abnormalities.

Purpose of the Study:

  • To review the primary mechanisms triggering drug-induced cholestasis.
  • To summarize existing in vitro systems for predicting drug cholestatic potential.
  • To provide mechanistic insights into drug-induced cholestasis.

Main Methods:

  • Literature review of drug-induced cholestasis mechanisms.
  • Survey of current in vitro models and technologies.
  • Analysis of predictive capabilities for drug cholestatic potential.

Main Results:

  • Identified key mechanisms of drug-induced cholestasis.
  • Cataloged various in vitro systems used for prediction.
  • Highlighted the need for advanced models to assess drug safety.

Conclusions:

  • Understanding drug-induced cholestasis mechanisms is crucial.
  • In vitro models are essential for predicting drug hepatotoxicity.
  • Further development of predictive technologies is required for safer drugs.
Keywords:
Drug-induced cholestasisIn vitroMechanismsPrediction

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