NDLI: Visualizing Compound Distribution during Zebrafish Embryo Development: The Effects of Lipophilicity and DMSO.

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Visualizing Compound Distribution during Zebrafish Embryo Development: The Effects of Lipophilicity and DMSO.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	de Koning, Coco Beekhuijzen, Manon Tobor-Kaplon, Marysia de Vries-Buitenweg, Selinda Schoutsen, Dick Leeijen, Nico Van De Waart, Beppy Emmen, Harry
Description	Country affiliation: Netherlands Author Affiliation: de Koning C ( WIL Research Europe B.V, Hambakenwetering 7, 's-Hertogenbosch, The Netherlands.); Beekhuijzen M ( WIL Research Europe B.V, Hambakenwetering 7, 's-Hertogenbosch, The Netherlands.); Tobor-Kaplon M ( WIL Research Europe B.V, Hambakenwetering 7, 's-Hertogenbosch, The Netherlands.); de Vries-Buitenweg S ( WIL Research Europe B.V, Hambakenwetering 7, 's-Hertogenbosch, The Netherlands.); Schoutsen D ( WIL Research Europe B.V, Hambakenwetering 7, 's-Hertogenbosch, The Netherlands.); Leeijen N ( WIL Research Europe B.V, Hambakenwetering 7, 's-Hertogenbosch, The Netherlands.); van de Waart B ( WIL Research Europe B.V, Hambakenwetering 7, 's-Hertogenbosch, The Netherlands.); Emmen H ( WIL Research Europe B.V, Hambakenwetering 7, 's-Hertogenbosch, The Netherlands.)
Abstract	The predictability of the zebrafish embryo model is highly influenced by internal exposure of the embryo/larva. As compound uptake is likely to be influenced by factors such as lipophilicity, solvent use, and chorion presence, this article focuses on investigating their effects on compound distribution within the zebrafish embryo. To visualize compound uptake and distribution, zebrafish embryos were exposed for 96 hr, starting at 4 hr postfertilization, to water-soluble dyes: Schiff's reagent (logP -4.63), Giemsa stain (logP -0.77), Van Gierson stain (logP 1.64), Cresyl fast violet (logP 3.5), Eosine Y (logP 4.8), Sudan III (logP 7.5), and Oil red O (logP 9.81), with and without 1% dimethyl-sulfoxide (DMSO). Three additional compounds were used to analytically determine the uptake and distribution: Acyclovir (logP -1.56), Zidovudine (logP 0.05), and Metoprolol Tartrate Salt (logP 1.8). Examinations were performed every 24 hr. Both methods (visualization and specific analysis) showed that exposure to higher logP values results in higher compound uptake. Specific analysis showed that for lipophilic compounds >90% of compound is taken up by the embryo. For hydrophilic compounds, >90% of compound within the complete egg could not be associated to embryo or chorion and is probably distributed into the perivitelline space. Overall, internal exposure analyses on at least two occasions (i.e., before and after hatching) is crucial for interpretation of zebrafish embryotoxicity data, especially for compounds with extreme logP values. DMSO did not affect exposure when examined with the visualization method, however, this method might be not sensitive enough to draw hard conclusions.
File Format	HTM / HTML
ISSN	15429733
Issue Number	6
Volume Number	104
e-ISSN	15429741
Journal	Birth Defects Research Part B: Developmental and Reproductive Toxicology
Language	English
Publisher	Wiley
Publisher Date	2015-12-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Teratology Discipline Toxicology Coloring Agents Metabolism Dimethyl Sulfoxide Pharmacology Embryo, Nonmammalian Embryonic Development Drug Effects Lipids Zebrafish Embryology Acyclovir Animals Chromatography, Liquid Larva Mass Spectrometry Metoprolol Ovum Solutions Zidovudine Journal Article
Content Type	Text
Resource Type	Article
Subject	Developmental Biology Health, Toxicology and Mutagenesis Toxicology Embryology

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