The zebrafish (Danio rerio) is a tropical fish with a genetic structure surprisingly similar to ours. However, they’ve become a popular model organism only relatively recently. ZeGlobalTox is a project collaboration making use of the zebrafish genetic structure to develop of an assay that is expected to be a medium/high-throughput preclinical zebrafish embryo screen. This screen will be capable of identifying compounds with potential organotoxicity liabilities in the same animal. Pivot Park Screening is beside ZeClinics and Noldus, one of the project partners. The outcomes of this project will positively affect the 3R principle (replace, reduce, refine) and therefore the ethical improvement of the use of animals for biomedical and pharmaceutical targets. The project is funded by the National Centre for Replacement, Refinement & Reduction of Animals in Research (NC3Rs) and the Spanish Ministry of Economy and Competitiveness (MINECO).
ZeGlobalTox will develop a quick and economical tool for assessing potential toxicities in large libraries of molecules at a morphological and functional level early in drug development. This tool has the potential to reduce the number of compounds entering regulatory in vivo studies and will reduce costly late stage attrition. The outcomes of this project will positively affect the 3R principle (replace, reduce, refine) and therefore improvement of the use of animals for biomedical and pharmaceutical targets.
The core principle of ZeGlobalTox is to extract reproducible results on acute toxicity, teratogenicity, cardio-, neuro- and hepato-toxicity in the same animal from microscope images of zebrafish embryos exposed to novel compounds. The entire process from treatment of the animals to image acquisition and analysis is automated, making the technology easy to adopt and integrate into existing testing strategies. In the context of the project a method will also be developed to analyze vascular toxicity, by video recording blood vessels and software-driven analyze blood flow and vessel diameters. The ZeGlobalTox platform uses zebrafish embryos younger than five days old and so are not protected animals requiring an ethical license.
Pivot Park Screening Centre will contribute by transferring the manual readout of zebrafish toxicity to an automated platform using the Operetta. Fluorescent or bright-field images and specific analytical software will be combined to extract information about the functionality of the organs or tissues in response to compounds. Furthermore, a number of compounds with known toxic effects will be provided and used as positive controls.