Development of novel tools for the in vitro investigation of drug-induced liver injury

Jian Jiang*, Jarno EJ Wolters, Simone G van Breda, Jos C Kleinjans, Theo M de Kok

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Due to its complex mechanisms and unpredictable occurrence, drug-induced liver injury (DILI) complicates drug identification and classification. Since species-specific differences in metabolism and pharmacokinetics exist, data obtained from animal studies may not be sufficient to predict DILI in humans.Areas covered: Over the last few decades, numerous in vitro models have been developed to replace animal testing. The advantages and disadvantages of commonly used liver-derived in vitro models (e.g., cell lines, hepatocyte models, liver slices, three-dimensional (3D) hepatospheres, etc.) are discussed. Toxicogenomics-based methodologies (genomics, epigenomics, transcriptomics, proteomics and metabolomics) and next-generation sequencing have also been used to enhance the reliability of DILI prediction. This review presents an overview of the currently used alternative toxicological models and of the most advanced approaches in the field of DILI research.Expert opinion: It seems unlikely that a...
Original languageEnglish
Pages (from-to)1523-1537
Number of pages15
JournalExpert Opinion on Drug Metabolism & Toxicology
Volume11
Issue number10
DOIs
Publication statusPublished - 3 Oct 2015

Keywords

  • -omics technologies
  • 3D culture
  • drug-induced liver injury
  • multicellular hepatospheres
  • primary hepatocytes
  • sequencing technologies
  • toxicogenomics

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