ZeTox

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PLATFORMS

icon-hepato-tox HepatoTox

Drug-induced liver injury (DILI) is a major cause of attrition during both the early and later stages of drug development and marketing process. 

Several mammalian liver toxicants cause liver injuries in larval zebrafish (1-2). Indeed, defensive mechanisms against xenobiotic chemicals, such as enzyme and oxidative stress induction, are equivalent in zebrafish and mammals, indicating that they may have analogous detoxification pathways

ZeClinics is able to assess the hepatotoxicity caused by the BMD of the molecule of interest in zebrafish larvae. This test can be carried out together with neuro- and cardiotoxicity assessment within the ZeGlobalTox protocol. It has been internally validated on 24 compounds against DMSO as a negative control (3).

Method description and readouts

Figure: HepatoTox method description and readouts

References

  1. Ung CY, Lam SH, Hlaing MM, Winata CL, Korzh S, et al. 2010. Mercury-induced hepatotoxicity in zebrafish: in vivo mechanistic insights from transcriptome analysis, phenotype anchoring and targeted gene expression validation. BMC Genomics.
  2. Hill A, Mesens N, Steemans M, Xu JJ, Aleo MD. 2012. Comparisons between in vitro whole cell imaging and in vivo zebrafish-based approaches for identifying potential human hepatotoxicants earlier in pharmaceutical development. Drug Metab Rev.
  3. Cornet et al. 2017 ZeGlobalTox - An Innovative Approach to Address Organ Drug Toxicity Using Zebrafish. J. Int. Mol. Sci.