Zebrafish as a New Model for Phenotype-based Screening of Positive Inotropic Agents

• Published in: Chemical biology & drug design Vol. 85; no. 3; pp. 253 - 258
• Main Authors: Tang, Chunlei, Xie, Desheng, Feng, Bainian
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.03.2015
• Subjects: Animals; Blood Pressure - drug effects; Cardiotonic Agents - chemistry; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Digoxin - chemistry; Digoxin - pharmacology; Digoxin - therapeutic use; Disease Models, Animal; Embryo, Nonmammalian - drug effects; Embryo, Nonmammalian - physiology; Heart - drug effects; Heart - physiology; heart failure; Heart Failure - chemically induced; Heart Failure - drug therapy; Heart Rate - drug effects; Male; Myocardium - pathology; Phenotype; phenotype-based; positive inotropic agent; Rats; Rats, Sprague-Dawley; Terfenadine - toxicity; zebrafish; Zebrafish - growth & development; phenotype-based; heart failure; zebrafish; positive inotropic agent
• ISSN: 1747-0277; 1747-0285
• DOI: 10.1111/cbdd.12389

The zebrafish‐based assay is a widely used animal model system for cardiovascular research. In this study, we investigated the cardiac defects caused by terfenadine and tested the pharmacological response of digoxin to zebrafish with cardiac defects. The study suggested that zebrafish could be a suitable model for phenotype‐based screening and evaluation of positive inotropic agents. This phenotype‐based heart failure zebrafish model system was then utilized in in‐house library screen. Some positive inotropic compound was discovered, which could attenuate the cardiac defects by increasing the flow velocity of caudal artery blood. In this study, we investigated the cardiac defects caused by terfenadine and tested the pharmacological response of digoxin to zebrafish with cardiac defects. The study suggested that zebrafish could be a suitable model for phenotype‐based screening and evaluation of positive inotropic agents. This phenotype‐based, heart failure zebrafish model system was then utilized in in‐house library screen. Some positive inotropic compound was discovered, which could attenuate the cardiac defects by increasing the flow velocity of caudal artery blood.