Kenn Foubert team manager

Research Kenn Foubert

Research team

Expertise

Qualitative and quantitative investigations on traditional and commercial available herbal products and food supplements. This implies the isolation, structure elucidation and activity measurements of compounds, next to the development and validation of analytical methods to preserve the quality of these products. In view of the possible increased activity of biological metabolites of these products, their content is also investigated after in-vitro gastro-intestinal and liver biotransformation, which gives the opportunity to identify the active metabolites. Next to this, the quality and content of skin products is investigated, with the identification of possible allergens as a result.

Advancing the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) towards a sensitive screening assay. 01/11/2020 - 31/10/2023

Abstract

Within Europe, alternative methods for toxicity assessment of xenobiotics become very important. Several pharmaceutical, agrochemical and cosmetic companies are currently using the zebrafish embryo as an alternative for animal testing to screen new compounds for developmental toxicity. However, false negative and false positive results are reported in the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) for known mammalian teratogens and non-teratogens, respectively. For safety, false negative results are more critical, as teratogens may be missed. This project aims to further refine the ZEDTA in order to increase the sensitivity of the assay and as such better predict birth defects caused by using drugs during the 1st trimester of pregnancy. In order to achieve this goal, first the number of evaluated morphological endpoints will be extended by including skeletal staining in the ZEDTA. Second, due to the intrinsically low biotransformation capacity of zebrafish embryos, a metabolic activation system will be developed in order to expose the zebrafish embryos not only to the parent compound but also to its potential teratogenic metabolite(s). Finally, additional morphological endpoints will be programmed in image analysis software that will be combined with an automated handling and imaging system. As such, this project will increase the sensitivity and throughput of the ZEDTA, resulting in better, faster and laboratory animal-free screening of teratogenic drugs.

Researcher(s)

Research team(s)

Project website

Project type(s)

  • Research Project

Advancing the zebrafish embryo developmental toxicity assay from screening to regulatory testing. 01/11/2019 - 31/10/2020

Abstract

Within Europe, alternative methods for toxicity assessment of xenobiotics become very important. Several pharmaceutical, agrochemical and cosmetic companies are currently using the zebrafish embryo as an alternative for animal testing to screen new compounds for developmental toxicity. However, false negative and false positive results are reported in the Zebrafish Embryo Developmental Toxicity Assay (ZEDTA) for known mammalian teratogens and non-teratogens, respectively. From a safety point of view, false negative results are more critical because teratogens may be missed by the assay. This project aims to further refine the ZEDTA protocol in order to increase the sensitivity of the assay and to advance the ZEDTA from screening towards potential regulatory acceptance. In order to achieve this goal, first the number of evaluated morphological endpoints will be extended by including skeletal staining in the ZEDTA. Second, due to the intrinsically low biotransformation capacity of zebrafish embryos, a metabolic activation system will be developed in order to expose the zebrafish embryos not only to the parent compound but also to its potential teratogenic metabolite(s). Finally, additional morphological endpoints will be programmed in image analysis software that will be combined with an automated handling and imaging system. As such, this project will increase the sensitivity and throughput of the ZEDTA for potential regulatory use.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project

Bioactivation of human proteratogens in the zebrafish embryo model, a potential alternative test for development toxicity assessment. 01/01/2018 - 31/12/2021

Abstract

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.

Researcher(s)

Research team(s)

Project type(s)

  • Research Project