Mechanisms and in vitro models of drug-induced cholestasis

Arch Toxicol. 2019 May;93(5):1169-1186. doi: 10.1007/s00204-019-02437-2. Epub 2019 Apr 10.

Abstract

Cholestasis underlies one of the major manifestations of drug-induced liver injury. Drug-induced cholestatic liver toxicity is a complex process, as it can be triggered by a variety of factors that induce 2 types of biological responses, namely a deteriorative response, caused by bile acid accumulation, and an adaptive response, aimed at removing the accumulated bile acids. Several key events in both types of responses have been characterized in the past few years. In parallel, many efforts have focused on the development and further optimization of experimental cell culture models to predict the occurrence of drug-induced cholestatic liver toxicity in vivo. In this paper, a state-of-the-art overview of mechanisms and in vitro models of drug-induced cholestatic liver injury is provided.

Keywords: Drug-induced cholestasis; In vitro models; Liver; Mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / physiopathology
  • Cholestasis / chemically induced*
  • Cholestasis / physiopathology
  • Drug-Related Side Effects and Adverse Reactions / physiopathology*
  • Humans
  • In Vitro Techniques

Substances

  • Bile Acids and Salts