PUBLICATION
Effects of bepridil on early cardiac development of zebrafish
- Authors
- Wei, Y.L., Lei, Y.Q., Ye, Z.J., Zhuang, X.D., Zhu, L.P., Wang, X.R., Cao, H.
- ID
- ZDB-PUB-221125-11
- Date
- 2022
- Source
- Cell and tissue research 391(2): 375-391 (Journal)
- Registered Authors
- Keywords
- Apoptosis, Bepridil, Cardiac development, Cardiotoxicity, Oxidative stress
- Datasets
- GEO:GSE193373
- MeSH Terms
-
- Myocytes, Cardiac/metabolism
- Rats
- Anti-Arrhythmia Agents/metabolism
- Anti-Arrhythmia Agents/pharmacology
- Animals
- Zebrafish*
- Bepridil*/metabolism
- Bepridil*/pharmacology
- Myocardium/metabolism
- PubMed
- 36422735 Full text @ Cell Tissue Res.
Citation
Wei, Y.L., Lei, Y.Q., Ye, Z.J., Zhuang, X.D., Zhu, L.P., Wang, X.R., Cao, H. (2022) Effects of bepridil on early cardiac development of zebrafish. Cell and tissue research. 391(2):375-391.
Abstract
Bepridil is a commonly used medication for arrhythmia and heart failure. It primarily exerts hemodynamic effects by inhibiting Na+/K+ movement and regulating the Na+/Ca2+ exchange. In comparison to other Ca2+ inhibitors, bepridil has a long half-life and a complex pharmacology. Additionally, it is widely used in antiviral research and the treatment of various diseases. However, the toxicity of this compound and its other possible effects on embryonic development are unknown. In this study, we investigated the toxicity of bepridil on rat myocardial H9c2 cells. After treatment with bepridil, the cells became overloaded with Ca2+ and entered a state of cytoplasmic vacuolization and nuclear abnormality. Bepridil treatment resulted in several morphological abnormalities in zebrafish embryo models, including pericardium enlargement, yolk sac swelling, and growth stunting. The hemodynamic effects on fetal development resulted in abnormal cardiovascular circulation and myocardial weakness. After inhibiting the Ca2+ transmembrane, the liver of zebrafish larvae also displayed an ectopic and deficient spatial location. Additionally, the results of the RNA-seq analysis revealed the detailed gene expression profiles and metabolic responses to bepridil treatment in zebrafish embryonic development. Taken together, our study provides an important evaluation of antiarrhythmic agents for clinical use in prenatal heart patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping