Bioactivation of human proteratogens in the zebrafish embryo model, a potential alternative test for development toxicity assessment.

Within Europe, alternative methods for toxicity assessment of xenobiotics become very important. For developmental toxicity, the mouse Embryonic Stem Cell test and the rat Whole Embryo Culture are commonly used, but assays in non-mammalian whole organisms are currently proposed as they more fully represent the complexity of early development. The zebrafish (Danio rerio) is one of the preferred species due to their small size, high fecundity and rapid ex utero development. However, knowledge on the ontogeny of biotransformation enzymes in this species remains scarce. This is a pivotal information, especially for proteratogens that require bioactivation to exert their teratogenic potential. The cytochrome P450 enzymes (CYPs) represent the most important enzyme family in this oxidative process and are also important for the (de) activation of endogenous molecules that regulate normal embryonic development. The aim of this research project is to assess the bioactivation capacity of zebrafish embryos by using molecular techniques that target specific CYP isoenzymes. As such, this project will show whether zebrafish embryos can bioactivate, and thus detect, proteratogens or not, which is key information when considering this alternative assay for developmental toxicity testing.

Keywords:CYTOCHROME, ZEBRAFISH, TERATOLOGY

Disciplines:Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences