Hepatotoxicity Screening on In Vitro Models and the Role of 'Omics

Joost van Delft*, Karen Mathijs, Jan Polman, Maarten Coonen, Ewa Szalowska, Geert R. Verheyen, Freddy van Goethem, Marja Driessen, Leo van de Ven, Sreenivasa Ramaiahgari, Leo S. Price

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

Abstract

The liver is one of the five most common target organs of toxicity, both during acute and chronic (repeated dose) toxicity, not only for drugs but also for cosmetic ingredients. Chemical entities can trigger liver damage in humans, and hepatotoxicity is the leading cause of withdrawal of drugs from the market, accounting for 40% of withdrawals worldwide. It has been estimated that only 50% of human liver toxicities could be predicted using animal models, and there is a clear need for accurately predictive toxicity and safety testing methods. Hepatocellular injury can manifest in a number of ways, including hepatitis, steatosis, cirrhosis, inflammation, phospholipidosis, and cholestasis. Cholestasis and steatosis are among the most prominent and well-documented types of liver injury and are the focus of this chapter. Furthermore, attention is also paid to necrosis, a mode of cell death that is observed in most of the aforementioned types of hepatocellular injury.

Original languageEnglish
Title of host publicationToxicogenomics-Based Cellular Models
Subtitle of host publicationAlternatives to Animal Testing for Safety Assessment
PublisherElsevier Inc. Academic Press
Chapter5.1
Pages193-212
Number of pages20
ISBN (Print)9780123978622
DOIs
Publication statusPublished - 2014

Keywords

  • Cholestasis
  • Hepatotoxicity
  • In vitro liver models
  • Necrosis
  • Steatosis

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