PUBLICATION
Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration
- Authors
- Guarin, M., Faelens, R., Giusti, A., De Croze, N., Léonard, M., Cabooter, D., Annaert, P., de Witte, P., Ny, A.
- ID
- ZDB-PUB-210611-1
- Date
- 2021
- Source
- Scientific Reports 11: 12229 (Journal)
- Registered Authors
- de Witte, Peter
- Keywords
- none
- MeSH Terms
-
- Alkynes/chemistry*
- Animals
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism*
- Fluorescent Dyes/administration & dosage*
- Fluorescent Dyes/pharmacokinetics*
- Microinjections/classification
- Microinjections/methods*
- Molecular Imaging/methods*
- Spatio-Temporal Analysis*
- Tissue Distribution
- Yolk Sac/metabolism
- Zebrafish
- PubMed
- 34108572 Full text @ Sci. Rep.
Citation
Guarin, M., Faelens, R., Giusti, A., De Croze, N., Léonard, M., Cabooter, D., Annaert, P., de Witte, P., Ny, A. (2021) Spatiotemporal imaging and pharmacokinetics of fluorescent compounds in zebrafish eleuthero-embryos after different routes of administration. Scientific Reports. 11:12229.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping