Journal Article

Effects of bepridil on early cardiac development of zebrafish

Ye, Zhou-Jie, Zhuang, Xu-Dong, Wei, Ya-Lan, Wang, Xin-Rui, Zhu, Li-Ping, Lei, Yu-Qing, Cao, Hua

2023

Overview

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 + /Ca 2+ exchange. In comparison to other Ca 2+ 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 Ca 2+ 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 Ca 2+ 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.

• Publisher: Springer Berlin Heidelberg,Springer,Springer Nature B.V
• Subject: Animals / Anti-Arrhythmia Agents - metabolism / Anti-Arrhythmia Agents - pharmacology / Antiarrhythmic agents / Antiviral agents / Antiviral drugs / Apoptosis / Arrhythmia / Bepridil / Bepridil - metabolism / Bepridil - pharmacology / Biomedical and Life Sciences / Biomedicine / Calcium / Congestive heart failure / Danio rerio / drug therapy / Embryogenesis / Embryonic development / Ethylenediaminetetraacetic acid / fetal development / Fetus / Fetuses / Gene expression / Growth / half life / heart / heart failure / Hemodynamics / Human Genetics / liver / Marburg virus disease / Medical research / Medicine, Experimental / Metabolic response / Molecular Medicine / Myocardium - metabolism / Myocytes, Cardiac - metabolism / Oxidative stress / Pericardium / pharmacology / Proteomics / Rats / Regular / Regular Article / RNA / sequence analysis / Toxicity / Yolk sac / Zebrafish