Paracetamol, Tenofovir, Tenofovir disoproxil fumarate Acetaminophen, Ampicillin, Indomethacin, Gentamicin, Kanamycin, Losartan, Penicillin G Prestwick chemical library, which includes 1285 off-patent tiny molecules, 95 authorized drugs 48 h (three dpf) Sensitivity 80 Specificity n.a. Sensitivity 100 Specificity n.a. Sensitivity 75 Specificity n.a. Sensitivity n.a. Specificity n.a. Partially (microinjection of gentamicin) No Predictivity Bioavailability EnsuredGorgulho et al., 2018 [75] Westhoff et al., 2013 [76] Westhoff et al., 2020 [77]24 h (4 dpf)24 h (248 hpf)No24 h (248 hpf) 42 h (68 hpf) 66 h (62 hpf) 90 h (66 hpf) 24 h (248 hpf) 48 h (242 hpf) 72 h (246 hpf)NoWu et al., 2012 [78]Citrinin, PatulinSensitivity one hundred Specificity n.a.No3.1. Cardiotoxicity The two-chambered ErbB3/HER3 drug embryonic zebrafish heart comprises 4 distinguishable structures: atrium, ventricle, sinus venosus and bulbus arteriosus [79,80]. It begins beating at 20 hpf [79]. At 24 hpf the heart tube is completed along with the division into two chambers happens at 48 hpf [81]. Valves, on the other hand, are not present at 48 hpf but create later till 5 dpf [80]. Since of this, regurgitation of your blood flow is possible throughout early life stages [82]. In spite of the early onset of heart function, blood circulation isn’t critical until 7 dpf, when the larvae’s will need for oxygen can no longer be covered solely by dermal diffusion [39]. This makes it possible for investigation of extreme cardiac phenotypes in zebrafish, which in rodent embryos would probably be lethal on account of lack of oxygen provide by circulatory dysfunction [83]. Mainly because of this, zebrafish embryos and larvae s potential to model ischemic cardiac events through embryonic stages might be principally limited. Despite this, measurements in adult zebrafish showed that the zebrafish electrocardiogram (ECG) is a lot more equivalent for the human ECG than that of rats and mice [70,84]. Further electrophysiological similarities were discovered in distinctive zebrafish mutants, e.g., using the discovery of zerg, a zebrafish ortholog of the hERG channel [85,86], that is a vital target in preclinical cardiotoxicity testing [87]. Due to this interspecies genetic and functional homology, impairment of heart function and morphology could be reproduced in embryonic zebrafish [88] soon after exposure to compounds recognized for their cardiotoxic effects in human clinical trials [89,90]. Examples of these compounds, not too long ago shown to become cardiotoxic in embryonic zebrafish, involve kinase inhibitors intended for chemotherapy [91,92], the antiarrhythmic drug verapamil [93] and the antihistamine terfenadine [94], which has been withdrawn in the industry because of potentially lethal ventricular arrhythmia triggered by prolongation on the QT interval [95]. Quite a few research (Table 1) help the model s fantastic sensitivity for cardiotoxicity, ranging in between 85 and one hundred [681]. The zebrafish heart functions the advantage of being visible and optically transparent all through embryonic and early larval stages. Thus, a plethora of non-invasive imaging assays, ranging from simple manual counting to Coccidia site large-scale automated imaging pipelines with corresponding application for evaluation, enable measurement in the embryonic zebrafish s heartbeat [69,9600]. However, based around the setup, anaesthesia for po-Int. J. Mol. Sci. 2021, 22,7 ofsitioning can pose a problem, as the typically applied anaesthetic tricaine (TMS, MS-222, Finquel, (3-aminobenzoic acidethyl ester methanesulfonate)) itself alters the embryo s heart functi