ZeTox – Toxicology Services

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icon-hepato-tox HepatoTox – Hepatotoxicology Services

Drug-induced liver injury is a major cause of attrition during both the early and later stages of drug development and marketing process. Reducing or eliminating drug-induced severe liver injury would be tremendously beneficial for patients. 

Zebrafish liver is fully developed and functional by 5 days post-fertilization. The use of zebrafish larvae for the assessment of compound-induced liver toxicity allows to streamline the process of drug evaluation and reduce the risk of drug attrition in the following phases of preclinical testing.

Advantages

The high correlation in defensive mechanisms against xenobiotic chemicals between zebrafish and mammals, indicating that they may have analogous detoxification pathways.

Metabolic experiments demonstrate that zebrafish embryos metabolize drugs similarly to humans.

Simultaneous assessment of cardiotoxicity and neurotoxicity through the service ZeGlobalTox.

Method description

Transgenic zebrafish larvae expressing red fluorescent protein in the hepatocytes are treated with the benchmark dose (BMD) of the compound of interest. Thereafter, fluorescent images of livers of larvae treated with control and test compounds are obtained. Finally, Oil Red O staining is performed to evaluate liver specific redouts.

Readouts

  • Liver area: Liver necrosis & hepatomegaly
  • Yolk lipid retention
  • Steatosis: fat accumulation in liver
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.
  4. A. D. Bastiaan Vliegenthart  Carl S. Tucker  Jorge Del Pozo  James W. Dear 2014. Zebrafish as model organisms for studying drug‐induced liver injury