In vitro assessment of hepatotoxicity by metabolomics: a review

Archives of Toxicology
Matthias CuykxAdrian Covaci

Abstract

Omics technologies, and in particular metabolomics, have received an increasing attention during the assessment of hepatotoxicity in vitro. However, at present, a consensus on good metabolomics practices has yet to be reached. Therefore, in this review, a range of experimental approaches, applied methodologies, and data processing workflows are compared and critically evaluated. Experimental designs among the studies are similar, reporting the use of primary hepatocytes or hepatic cell lines as the most frequently used cell sources. Experiments are usually conducted in short time-frames (< 48 h) at sub-toxic dosages. Applied sample preparations are protein precipitation or Bligh-and-Dyer extraction. Most analytical platforms rely on chromatographic separations with mass spectrometric detection using high-resolution instruments. Untargeted metabolomics was typically used to allow the simultaneous detection of several classes of the metabolome, including endogenous metabolites that are not initially linked to toxicity. This non-biased detection platform is a valuable tool for generating hypothesis-based mechanistic research. The most frequently reported metabolites that are altered under toxicological impulses are alanine, lactat...Continue Reading

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Citations

May 28, 2019·Analytical and Bioanalytical Chemistry·Lisa EisenbeissThomas Kraemer
Jul 12, 2019·Expert Opinion on Drug Metabolism & Toxicology·Yvonne GloorCaroline F Samer
Jul 17, 2020·Frontiers in Pharmacology·Hong FengYuan-Fu Lu
Apr 16, 2021·Frontiers in Medicine·Shuai-Shuai ChenJia-Bo Wang
May 9, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yusha LuoTingting Zhou

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Methods Mentioned

BETA
scraping
PCA
NMR
nuclear magnetic resonance

Software Mentioned

IMPaLA
Ingenuity Pathway analysis
MOA
MetaboAnalyst

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