Zebrafish Cardiotoxicity Assays

Cardiotoxicity is defined as the toxicity that damages the heart muscle and other cardiac tissues or disrupts the electrophysiology of the heart. Drug-induced cardiotoxicity is not limited to a specific therapeutic area. Almost every therapeutic class of drugs has produced unexpected cardiotoxicities, including anthracyclines (ANTs) and other anticancer agents, antibacterials, antifungals, antiretrovirals, psychotropics and antihistamines. Currently, the early prediction for cardiotoxicity has become an important issue in new drug research and development. Thus, alternative animal models and methods for drug safety evaluation have been given great attention.

The zebrafish (Danio rerio) is a useful animal model system for studying genetics, cardiovascular development, and cardiotoxicity. Recently, extensive chemical and drug toxicity screening have been conducted using zebrafish embryos. Relevance and predictability of drug response between zebrafish and humans have been studied, and it has been found that zebrafish show a high percentage of predictability (78% and 70%) of drug response. Both the mammalian and zebrafish heart share the development of specialized chambers, valves to ensure directionality, outflow tracts to an intricate vasculature, specialized endothelial cells to drive a high-pressure system, and an electrical system to regulate the rhythm. Besides, cardiac performance in adult zebrafish can be detected by new noninvasive methods. It can be assessed by advancing conventional echocardiography with speckle-tracking analyses and changes in cardiac performance, and allows highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution.

Representative images of zebrafish in the embryonic cardiac assay (at 72 hpf).Figure 1. Representative images of zebrafish in the embryonic cardiac assay (at 72 hpf).

Our Cardiotoxicity Evaluation in Zebrafish

Creative Biogene can utilize zebrafish models to help you explore reliable detection parameters for drug-induced cardiotoxicity evaluation. Our services contribute to improving the understanding of drug-induced cardiotoxicity, and providing an easy in vivo model for screening drug candidates for cardiotoxicity in the early phase of drug development.

We have a package of evaluation endpoints:

  • Lethality
  • Morphological change of the heart
  • Heart rate assessment
  • Rhythmicity
  • Circulation
  • Pericardial Edema
  • Hemorrhage/Thrombosis
  • Heart-specific gene and protein expression

Our Advantages

  • Wide ranges of detection technologies
  • Easy and flexible workflow
  • Advanced high-content screening equipment
  • Excellent predictability

Contact us to learn more about how we can evaluate the cardiotoxicity potential of your candidates.

References

  1. Han Y, et al. Cardiotoxicity evaluation of anthracyclines in zebrafish (Danio rerio). Journal of Applied Toxicology, 2015, 35(3): 241-252.
  2. Zakaria Z Z, et al. Using zebrafish for investigating the molecular mechanisms of drug-induced cardiotoxicity. BioMed research international, 2018, 2018.
  3. Mcgrath P. 4. Assessment of Drug-Induced Cardiotoxicity in Zebrafish. Zebrafish: Methods for Assessing Drug Safety and Toxicity. 2011.
  4. Caballero M V, Candiracci M. Zebrafish as screening model for detecting toxicity and drugs efficacy. Journal of Unexplored Medical Data, 2018, 3(4): 1-14.
  5. Dyballa S, et al. Comparison of Zebrafish Larvae and hiPSC Cardiomyocytes for Predicting Drug-Induced Cardiotoxicity in Humans. Toxicological Sciences, 2019, 171(2): 283-295.

For research use only. Not intended for any clinical use.

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