Using Zebrafish for Investigating the Molecular Mechanisms of Drug-Induced Cardiotoxicity

Abstract

Over the last decade, the zebrafish (Danio rerio) has emerged as a model organism for cardiovascular research. Zebrafish have several advantages over mammalian models. For instance, the experimental cost of using zebrafish is comparatively low; the embryos are transparent, develop externally, and have high fecundity making them suitable for large-scale genetic screening. More recently, zebrafish embryos have been used for the screening of a variety of toxic agents, particularly for cardiotoxicity testing. Zebrafish has been shown to exhibit physiological responses that are similar to mammals after exposure to medicinal drugs including xenobiotics, hormones, cancer drugs, and also environmental pollutants, including pesticides and heavy metals. In this review, we provided a summary for recent studies that have used zebrafish to investigate the molecular mechanisms of drug-induced cardiotoxicity. More specifically, we focused on the techniques that were exploited by us and others for cardiovascular toxicity assessment and described several microscopic imaging and analysis protocols that are being used for the estimation of a variety of cardiac hemodynamic parameters.

Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants

“…Teratology is the study of unusual growth, and a teratogen is any substance that triggers the production of a congenital anomaly or enhances the occurrence of a specific hereditary deficiency [ 53 ]. Screening for teratogenicity includes introducing zebrafish embryos to the required concentration of the compound of interest, and it has become a popular model for analyzing the teratogenic effects of medicines [ 35 ]. Teratological and embryo-toxic effects are easy to detect due to the transparency of zebrafish embryos during their growth outside of their parent [ 54 ].…”

“…Small molecules may be introduced directly into the water in multi-well racks, where fish take them up via diffusion. The researched drugs can also be injected into the yolk sac [ 35 ]. Thus, the zebrafish is a great model for studying the premature embryonic diet on toxicants [ 36 ].…”

AEO-7 Surfactant is “super Toxic” and Induces Severe Cardiac, Liver and Locomotion Damage in Zebrafish Embryos

“…Since different organs of the zebra sh become fully functional at different stages [26], acute toxicity, cardiotoxicity, and hematopoiesis were assessed once every 24 h for three days after initiating exposure at 24 hpf, and central nervous system (CNS) toxicity and hepatotoxicity following treatment from 96-120 hpf, as illustrated in Fig 1 [24,25,27,[35][36][37][38][39]. During early embryogenesis the protective chorion envelope around the embryos might interfere with uptake of the compounds being tested.…”

“…Zebra sh have proven to be an excellent model for studying the cardiotoxic effects of xenobiotics [27,38], with an overall success rate for predicting cardiotoxic and non-cardiotoxic drugs of 100% according to some investigators [60,61] and a rating of excellent (>85%) for identifying cardiovascular toxins based on the criteria proposed by the European Center for the Validation of Alternative Methods [61]. The dorsal aorta (DA), the major axial artery in the trunk, is one of the vessels that forms rst during the early development of all vertebrates.…”

Pestisit indüklü kardiyak toksisite araştırmalarında zebra balığı (Danio rerio)

“…Örneğin; bir trisiklik antidepresan olan Clomipramine, insanda uzamış QT aralığına yol açarken zebra balıklarında perikardiyal ödem, hemoraji, bradikardi ve yüksek konsantrasyonlarda ise ölüme neden olmuştur [62]. Sodyum kanal blokeri antiaritmik Mexiletine uygulamasının ise hem insanda hem de zebra balığında kalp atım sayısında azalmaya yol açtığı bildirilmiştir [63].…”