Abstract
Prerequisite to any biological laboratory assay employing living animals is consideration about its necessity, feasibility, ethics and the potential harm caused during an experiment. The imperative of these thoughts has led to the formulation of the 3R-principle, which today is a pivotal scientific standard of animal experimentation worldwide. The rising amount of laboratory investigations utilizing living animals throughout the last decades, either for regulatory concerns or for basic science, demands the development of alternative methods in accordance with 3R to help reduce experiments in mammals. This demand has resulted in investigation of additional vertebrate species displaying favourable biological properties. One prominent species among these is the zebrafish (Danio rerio), as these small laboratory ray-finned fish are well established in science today and feature outstanding biological characteristics. In this review, we highlight the advantages and general prerequisites of zebrafish embryos and larvae before free-feeding stages for toxicological testing, with a particular focus on cardio-, neuro, hepato- and nephrotoxicity. Furthermore, we discuss toxicokinetics, current advances in utilizing zebrafish for organ toxicity testing and highlight how advanced laboratory methods (such as automation, advanced imaging and genetic techniques) can refine future toxicological studies in this species.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Prerequisite to any biological assay utilizing animals is consideration about its necessity, feasibility, ethics and the potential harm caused. The imperative of these thoughts has led to the formulation of the 3R-principle [1], which today is well accepted as a scientific standard and which has been implemented in the legislation framework of animal experimentation worldwide
Further electrophysiological similarities were found in different zebrafish mutants, e.g., with the discovery of zerg, a zebrafish ortholog of the hERG channel [85,86], which is an important target in preclinical cardiotoxicity testing [87]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The rising amount of experimentation utilizing animals throughout the last decades demands the active development of alternative methods and assays. Prerequisite to any biological assay utilizing animals is consideration about its necessity, feasibility, ethics and the potential harm caused. The imperative of these thoughts has led to the formulation of the 3R-principle [1], which today is well accepted as a scientific standard and which has been implemented in the legislation framework of animal experimentation worldwide. In recent years the necessity of adequate alternatives especially to mammals and higher vertebrates for regulatory safety testing has resulted in raised scientific interest to establish methods in a variety of species displaying biological properties more suitable for specific scientific investigations. One large group among these alternatives are ray-finned fish (Actinopterygii), comprising an enormous amount of approximately 30,000 different species including well-known laboratory fish species such as zebrafish
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