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Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration
Zebrafish (Danio rerio) is increasingly used to assess the pharmacological activity and toxicity of compounds. The spatiotemporal distribution of seven fluorescent alkyne compounds was examined during 48 h after immersion (10 µM) or microinjection (2 mg/kg) in the pericardial cavity (PC), intraperit...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190279/ https://www.ncbi.nlm.nih.gov/pubmed/34108572 http://dx.doi.org/10.1038/s41598-021-91612-6 |
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author | Guarin, Marlly Faelens, Ruben Giusti, Arianna De Croze, Noémie Léonard, Marc Cabooter, Deirdre Annaert, Pieter de Witte, Peter Ny, Annelii |
author_facet | Guarin, Marlly Faelens, Ruben Giusti, Arianna De Croze, Noémie Léonard, Marc Cabooter, Deirdre Annaert, Pieter de Witte, Peter Ny, Annelii |
author_sort | Guarin, Marlly |
collection | PubMed |
description | Zebrafish (Danio rerio) is increasingly used to assess the pharmacological activity and toxicity of compounds. The spatiotemporal distribution of seven fluorescent alkyne compounds was examined during 48 h after immersion (10 µM) or microinjection (2 mg/kg) in the pericardial cavity (PC), intraperitoneally (IP) and yolk sac (IY) of 3 dpf zebrafish eleuthero-embryos. By modelling the fluorescence of whole-body contours present in fluorescence images, the main pharmacokinetic (PK) parameter values of the compounds were determined. It was demonstrated that especially in case of short incubations (1–3 h) immersion can result in limited intrabody exposure to compounds. In this case, PC and IP microinjections represent excellent alternatives. Significantly, IY microinjections did not result in a suitable intrabody distribution of the compounds. Performing a QSPkR (quantitative structure-pharmacokinetic relationship) analysis, LogD was identified as the only molecular descriptor that explains the final uptake of the selected compounds. It was also shown that combined administration of compounds (immersion and microinjection) provides a more stable intrabody exposure, at least in case of a prolonged immersion and compounds with LogD value > 1. These results will help reduce the risk of false negative results and can offer an invaluable input for future translational research and safety assessment applications. |
format | Online Article Text |
id | pubmed-8190279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81902792021-06-10 Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration Guarin, Marlly Faelens, Ruben Giusti, Arianna De Croze, Noémie Léonard, Marc Cabooter, Deirdre Annaert, Pieter de Witte, Peter Ny, Annelii Sci Rep Article Zebrafish (Danio rerio) is increasingly used to assess the pharmacological activity and toxicity of compounds. The spatiotemporal distribution of seven fluorescent alkyne compounds was examined during 48 h after immersion (10 µM) or microinjection (2 mg/kg) in the pericardial cavity (PC), intraperitoneally (IP) and yolk sac (IY) of 3 dpf zebrafish eleuthero-embryos. By modelling the fluorescence of whole-body contours present in fluorescence images, the main pharmacokinetic (PK) parameter values of the compounds were determined. It was demonstrated that especially in case of short incubations (1–3 h) immersion can result in limited intrabody exposure to compounds. In this case, PC and IP microinjections represent excellent alternatives. Significantly, IY microinjections did not result in a suitable intrabody distribution of the compounds. Performing a QSPkR (quantitative structure-pharmacokinetic relationship) analysis, LogD was identified as the only molecular descriptor that explains the final uptake of the selected compounds. It was also shown that combined administration of compounds (immersion and microinjection) provides a more stable intrabody exposure, at least in case of a prolonged immersion and compounds with LogD value > 1. These results will help reduce the risk of false negative results and can offer an invaluable input for future translational research and safety assessment applications. Nature Publishing Group UK 2021-06-09 /pmc/articles/PMC8190279/ /pubmed/34108572 http://dx.doi.org/10.1038/s41598-021-91612-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Guarin, Marlly Faelens, Ruben Giusti, Arianna De Croze, Noémie Léonard, Marc Cabooter, Deirdre Annaert, Pieter de Witte, Peter Ny, Annelii Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration |
title | Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration |
title_full | Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration |
title_fullStr | Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration |
title_full_unstemmed | Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration |
title_short | Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration |
title_sort | spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190279/ https://www.ncbi.nlm.nih.gov/pubmed/34108572 http://dx.doi.org/10.1038/s41598-021-91612-6 |
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