Mechanisms and in vitro models of drug-induced cholestasis

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 accumulat...

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Bibliographic Details
Published in:Archives of toxicology 2019-05, Vol.93 (5), p.1169-1186
Main Authors: Gijbels, Eva, Vilas-Boas, Vânia, Deferm, Neel, Devisscher, Lindsey, Jaeschke, Hartmut, Annaert, Pieter, Vinken, Mathieu
Format: Article
Language:English
Subjects:
Acids
Bile
Bile acids
Biocompatibility
Biomedical and Life Sciences
Biomedicine
Cell culture
Cholestasis
Environmental Health
Gallbladder diseases
Liver
Occupational Medicine/Industrial Medicine
Optimization
Pharmacology/Toxicology
Review Article
Toxicity
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Summary: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.
ISSN:0340-5761
1432-0738
DOI:10.1007/s00204-019-02437-2