Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Guarin, Marlly, Faelens, Ruben, Giusti, Arianna, De Croze, Noémie, Léonard, Marc, Cabooter, Deirdre, Annaert, Pieter, de Witte, Peter, Ny, Annelii
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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
_version_ 1783705652935262208
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
work_keys_str_mv AT guarinmarlly spatiotemporalimagingandpharmacokineticsoffluorescentcompoundsinzebrafisheleutheroembryosafterdifferentroutesofadministration
AT faelensruben spatiotemporalimagingandpharmacokineticsoffluorescentcompoundsinzebrafisheleutheroembryosafterdifferentroutesofadministration
AT giustiarianna spatiotemporalimagingandpharmacokineticsoffluorescentcompoundsinzebrafisheleutheroembryosafterdifferentroutesofadministration
AT decrozenoemie spatiotemporalimagingandpharmacokineticsoffluorescentcompoundsinzebrafisheleutheroembryosafterdifferentroutesofadministration
AT leonardmarc spatiotemporalimagingandpharmacokineticsoffluorescentcompoundsinzebrafisheleutheroembryosafterdifferentroutesofadministration
AT cabooterdeirdre spatiotemporalimagingandpharmacokineticsoffluorescentcompoundsinzebrafisheleutheroembryosafterdifferentroutesofadministration
AT annaertpieter spatiotemporalimagingandpharmacokineticsoffluorescentcompoundsinzebrafisheleutheroembryosafterdifferentroutesofadministration
AT dewittepeter spatiotemporalimagingandpharmacokineticsoffluorescentcompoundsinzebrafisheleutheroembryosafterdifferentroutesofadministration
AT nyannelii spatiotemporalimagingandpharmacokineticsoffluorescentcompoundsinzebrafisheleutheroembryosafterdifferentroutesofadministration