Related Experiment Video
Updated: Oct 11, 2025
High-Frequency Ultrasound Echocardiography to Assess Zebrafish Cardiac Function
Published on: March 12, 2020
Evaluation of β-adrenergic ligands for development of pharmacological heart failure and transparency models in
Monika Maciag1, Artur Wnorowski2, Kinga Bednarz2
1Department of Biopharmacy, Medical University of Lublin, 4a Chodzki Street, 20-093 Lublin, Poland; Independent Laboratory of Behavioral Studies, Medical University of Lublin, 4a Chodzki Street, 20-093 Lublin, Poland.
Abstract:
Cardiovascular toxicity represents one of the most common reasons for clinical trial failure. Consequently, early identification of novel cardioprotective strategies could prevent the later-stage drug-induced cardiac side effects. The use of zebrafish (Danio rerio) in preclinical studies has greatly increased. High-throughput and low-cost of assays make zebrafish model ideal for initial drug discovery. A common strategy to induce heart failure is a chronic β-adrenergic (βAR) stimulation. Herein, we set out to test a panel of βAR agonists to develop a pharmacological heart failure model in zebrafish. We assessed βAR agonists with respect to the elicited mortality, changes in heart rate, and morphological alterations in zebrafish larvae according to Fish Embryo Acute Toxicity Test. Among the tested βAR agonists, epinephrine elicited the most potent onset of heart stimulation (EC50 = 0.05 mM), which corresponds with its physiological role as catecholamine. However, when used at ten-fold higher dose (0.5 mM), the same compound caused severe heart rate inhibition (-28.70 beats/min), which can be attributed to its cardiotoxicity. Further studies revealed that isoetharine abolished body pigmentation at the sublethal dose of 7.50 mM. Additionally, as a proof of concept that zebrafish can mimic human cardiac physiology, we tested βAR antagonists (propranolol, carvedilol, metoprolol, and labetalol) and verified that they inhibited fish heart rate in a similar fashion as in humans. In conclusion, we proposed two novel pharmacological models in zebrafish; i.e., epinephrine-dependent heart failure and isoetharine-dependent transparent zebrafish. We provided strong evidence that the zebrafish model constitutes a valuable tool for cardiovascular research.
Insights
Zebrafish models can identify drug-induced heart failure and transparency. Epinephrine caused heart issues, while isoetharine induced transparency, proving zebrafish utility in cardiovascular research.
Area of Science:
- Cardiovascular toxicology and drug discovery
- Zebrafish (Danio rerio) as a model organism
Background:
- Cardiovascular toxicity is a major cause of clinical trial failure, necessitating early identification of cardioprotective strategies.
- Zebrafish offer a high-throughput, low-cost model ideal for preclinical drug discovery and toxicity screening.
- Chronic beta-adrenergic receptor (βAR) stimulation is a common method to induce heart failure.
Purpose of the Study:
- To develop novel pharmacological models for heart failure and drug-induced side effects using zebrafish.
- To evaluate a panel of βAR agonists for their potential to induce cardiotoxicity and other effects in zebrafish.
- To validate the use of zebrafish as a model for human cardiac physiology by testing βAR antagonists.
Main Methods:
- Zebrafish larvae were exposed to various βAR agonists and antagonists.
- Assays included mortality, heart rate, and morphological change assessments based on the Fish Embryo Acute Toxicity Test.
- Pharmacological responses were compared to known human physiological effects.
Main Results:
- Epinephrine demonstrated potent heart stimulation (EC50 = 0.05 mM) but induced cardiotoxicity at higher doses (0.5 mM), causing significant heart rate inhibition.
- Isoetharine at a sublethal dose (7.50 mM) resulted in abolished body pigmentation, creating transparent zebrafish.
- Tested βAR antagonists (propranolol, carvedilol, metoprolol, labetalol) inhibited zebrafish heart rate similarly to humans.
Conclusions:
- Two novel pharmacological models were proposed: epinephrine-induced heart failure and isoetharine-induced transparent zebrafish.
- The study provides strong evidence for the zebrafish model's value in cardiovascular research and early drug toxicity screening.
- Zebrafish effectively mimic human cardiac physiology, supporting their use in developing cardioprotective strategies.
