ZeTox – Toxicology Services

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icon-cardio-tox CardioTox – Cardiotoxicology Services

Cardiotoxicity is among the most common causes for clinical and post-market drug attrition. Thus, an early (and predictive) assessment of drug-induced cardiotoxicity is essential during the drug development process. Zebrafish is a strong alternative model for drug cardiotoxicity assessment, as we demonstrated in our paper.

Advantages

A high correlation between zebrafish larvae and clinical cardiotoxic data (PPV=86%; NPV=57%).

These predictive values are in line with those obtained when using the dog model, the gold-standard in vivo model for cardiotoxicity prediction.

In line with that, the comparison between the zebrafish larvae and the in vitro hERG models revealed a strong correlation (R2 = 0.714).

Simultaneous assessment of Neurotoxicity and hepatotoxicity through the service ZeGlobalTox.

Method description

ZeCardio™ is a fully automatized drug-screening platform that integrates image acquisition and analysis tools developed by ZeClinics. The platform allows the quantification of relevant cardiovascular parameters in zebrafish larvae, allowing the prediction of drug-induced cardiovascular liabilities in humans, with only 4-hours drug incubation. 

Figure: The platform has been validated on 92 compounds, with a known target and cardiotoxic activity in humans, to provide a comprehensive comparison of drug-induced cardiotoxicity in humans with data from zebrafish larvae.

Readouts

Determination of relevant parameters related to the cardiac function at 120 hpf:

  • Heartbeat frequency (ventricle and atrium)
  • Arrhythmias
  • Ejection fraction
  • QT prolongation
  • Fibrillation
  • Cardiac arrest

References

  1. Dyballa S et al. 2019. Comparison of Zebrafish Larvae and hiPSC Cardiomyocytes for Predicting Drug-Induced Cardiotoxicity in Humans. Toxicological Sciences
  2. Dingsheng Wen, Aiming Liu, Feng Chen, Julin Yang and Renke Dai. 2012. Validation of visualized transgenic zebrafish as a high throughput model to assay Bradycardia related cardio toxicity risk candidates. Journal of App. Tox.
  3. Shin JT, Pomerantsev EV, Mably JD, MacRae CA. 2010. High-resolution cardiovascular function confirms functional orthology of myocardial contractility pathways in zebrafish. Physiol. Genomics.