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Pharmacokinetics in Zebrafish Embryos (ZFE) Following Immersion and Intrayolk Administration: A Fluorescence-Based Analysis

Zebrafish embryos (ZFE) have increasingly gained in popularity as a model to perform safety screenings of compounds. Although immersion of ZFE is the main route of exposure used, evidence shows that not all small molecules are equally absorbed, possibly resulting in false-negative readouts and incor...

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Autores principales: Guarin, Marlly, Ny, Annelii, De Croze, Noémie, Maes, Jan, Léonard, Marc, Annaert, Pieter, de Witte, Peter A. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234359/
https://www.ncbi.nlm.nih.gov/pubmed/34208572
http://dx.doi.org/10.3390/ph14060576
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author Guarin, Marlly
Ny, Annelii
De Croze, Noémie
Maes, Jan
Léonard, Marc
Annaert, Pieter
de Witte, Peter A. M.
author_facet Guarin, Marlly
Ny, Annelii
De Croze, Noémie
Maes, Jan
Léonard, Marc
Annaert, Pieter
de Witte, Peter A. M.
author_sort Guarin, Marlly
collection PubMed
description Zebrafish embryos (ZFE) have increasingly gained in popularity as a model to perform safety screenings of compounds. Although immersion of ZFE is the main route of exposure used, evidence shows that not all small molecules are equally absorbed, possibly resulting in false-negative readouts and incorrect conclusions. In this study, we compared the pharmacokinetics of seven fluorescent compounds with known physicochemical properties that were administered to two-cell stage embryos by immersion or by IY microinjection. Absorption and distribution of the dyes were followed at various timepoints up to 120 hpf by spatiotemporal fluorescence imaging. The concentration (10 µM) and dose (2 mg/kg) used were selected as quantities typically applied in preclinical experiments and zebrafish studies. The data show that in the case of a lipophilic compound (log D: 1.73) the immersion procedure resulted in an intrabody exposure which is similar or higher than that seen after the IY microinjection. In contrast, zero to low intrabody exposure was reached after immersion of the embryos with less lipophilic compounds. In the latter case IY microinjection, a technical procedure that can be easily automated, is highly recommended.
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spelling pubmed-82343592021-06-27 Pharmacokinetics in Zebrafish Embryos (ZFE) Following Immersion and Intrayolk Administration: A Fluorescence-Based Analysis Guarin, Marlly Ny, Annelii De Croze, Noémie Maes, Jan Léonard, Marc Annaert, Pieter de Witte, Peter A. M. Pharmaceuticals (Basel) Article Zebrafish embryos (ZFE) have increasingly gained in popularity as a model to perform safety screenings of compounds. Although immersion of ZFE is the main route of exposure used, evidence shows that not all small molecules are equally absorbed, possibly resulting in false-negative readouts and incorrect conclusions. In this study, we compared the pharmacokinetics of seven fluorescent compounds with known physicochemical properties that were administered to two-cell stage embryos by immersion or by IY microinjection. Absorption and distribution of the dyes were followed at various timepoints up to 120 hpf by spatiotemporal fluorescence imaging. The concentration (10 µM) and dose (2 mg/kg) used were selected as quantities typically applied in preclinical experiments and zebrafish studies. The data show that in the case of a lipophilic compound (log D: 1.73) the immersion procedure resulted in an intrabody exposure which is similar or higher than that seen after the IY microinjection. In contrast, zero to low intrabody exposure was reached after immersion of the embryos with less lipophilic compounds. In the latter case IY microinjection, a technical procedure that can be easily automated, is highly recommended. MDPI 2021-06-16 /pmc/articles/PMC8234359/ /pubmed/34208572 http://dx.doi.org/10.3390/ph14060576 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guarin, Marlly
Ny, Annelii
De Croze, Noémie
Maes, Jan
Léonard, Marc
Annaert, Pieter
de Witte, Peter A. M.
Pharmacokinetics in Zebrafish Embryos (ZFE) Following Immersion and Intrayolk Administration: A Fluorescence-Based Analysis
title Pharmacokinetics in Zebrafish Embryos (ZFE) Following Immersion and Intrayolk Administration: A Fluorescence-Based Analysis
title_full Pharmacokinetics in Zebrafish Embryos (ZFE) Following Immersion and Intrayolk Administration: A Fluorescence-Based Analysis
title_fullStr Pharmacokinetics in Zebrafish Embryos (ZFE) Following Immersion and Intrayolk Administration: A Fluorescence-Based Analysis
title_full_unstemmed Pharmacokinetics in Zebrafish Embryos (ZFE) Following Immersion and Intrayolk Administration: A Fluorescence-Based Analysis
title_short Pharmacokinetics in Zebrafish Embryos (ZFE) Following Immersion and Intrayolk Administration: A Fluorescence-Based Analysis
title_sort pharmacokinetics in zebrafish embryos (zfe) following immersion and intrayolk administration: a fluorescence-based analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234359/
https://www.ncbi.nlm.nih.gov/pubmed/34208572
http://dx.doi.org/10.3390/ph14060576
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