Evaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.

Zebrafish are rapidly growing in popularity as an in vivo model system for chemical genetics, drug discovery, and toxicology, and more recently also for natural product discovery. Experiments involving the pharmacological evaluation of small molecules or natural product extracts in zebrafish bioassa...

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Autores principales:	Jan Maes, Lien Verlooy, Olivia E Buenafe, Peter A M de Witte, Camila V Esguerra, Alexander D Crawford
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c751d6051ab4ecd8a668a7e0507e8fb
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spelling	oai:doaj.org-article:9c751d6051ab4ecd8a668a7e0507e8fb2021-11-18T08:11:46ZEvaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.1932-620310.1371/journal.pone.0043850https://doaj.org/article/9c751d6051ab4ecd8a668a7e0507e8fb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23082109/?tool=EBIhttps://doaj.org/toc/1932-6203Zebrafish are rapidly growing in popularity as an in vivo model system for chemical genetics, drug discovery, and toxicology, and more recently also for natural product discovery. Experiments involving the pharmacological evaluation of small molecules or natural product extracts in zebrafish bioassays require the effective delivery of these compounds to embryos and larvae. While most samples to be screened are first solubilized in dimethyl sulfoxide (DMSO), which is then diluted in the embryo medium, often this method is not sufficient to prevent the immediate or eventual precipitation of the sample. Certain compounds and extracts are also not highly soluble in DMSO. In such instances the use of carriers and/or other solvents might offer an alternative means to achieve the required sample concentration. Towards this end, we determined the maximum tolerated concentration (MTC) of several commonly used solvents and carriers in zebrafish embryos and larvae at various developmental stages. Solvents evaluated for this study included acetone, acetonitrile, butanone, dimethyl formamide, DMSO, ethanol, glycerol, isopropanol, methanol, polyethylene glycol (PEG-400), propylene glycol, and solketal, and carriers included albumin (BSA) and cyclodextrin (2-hydroxypropyl-beta-cyclodextrin, or HPBCD). This study resulted in the identification of polyethylene glycol (PEG400), propylene glycol, and methanol as solvents that were relatively well-tolerated over a range of developmental stages. In addition, our results showed that acetone was well-tolerated by embryos but not by larvae, and 1% cyclodextrin (HPBCD) was well-tolerated by both embryos and larvae, indicating the utility of this carrier for compound screening in zebrafish. However, given the relatively small differences (2-3 fold) between concentrations that are apparently safe and those that are clearly toxic, further studies - e.g. omics analyses -should be carried out to determine which cellular processes and signalling pathways are affected by any solvents and carriers that are used for small-molecule screens in zebrafish.Jan MaesLien VerlooyOlivia E BuenafePeter A M de WitteCamila V EsguerraAlexander D CrawfordPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e43850 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jan Maes Lien Verlooy Olivia E Buenafe Peter A M de Witte Camila V Esguerra Alexander D Crawford Evaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.
description	Zebrafish are rapidly growing in popularity as an in vivo model system for chemical genetics, drug discovery, and toxicology, and more recently also for natural product discovery. Experiments involving the pharmacological evaluation of small molecules or natural product extracts in zebrafish bioassays require the effective delivery of these compounds to embryos and larvae. While most samples to be screened are first solubilized in dimethyl sulfoxide (DMSO), which is then diluted in the embryo medium, often this method is not sufficient to prevent the immediate or eventual precipitation of the sample. Certain compounds and extracts are also not highly soluble in DMSO. In such instances the use of carriers and/or other solvents might offer an alternative means to achieve the required sample concentration. Towards this end, we determined the maximum tolerated concentration (MTC) of several commonly used solvents and carriers in zebrafish embryos and larvae at various developmental stages. Solvents evaluated for this study included acetone, acetonitrile, butanone, dimethyl formamide, DMSO, ethanol, glycerol, isopropanol, methanol, polyethylene glycol (PEG-400), propylene glycol, and solketal, and carriers included albumin (BSA) and cyclodextrin (2-hydroxypropyl-beta-cyclodextrin, or HPBCD). This study resulted in the identification of polyethylene glycol (PEG400), propylene glycol, and methanol as solvents that were relatively well-tolerated over a range of developmental stages. In addition, our results showed that acetone was well-tolerated by embryos but not by larvae, and 1% cyclodextrin (HPBCD) was well-tolerated by both embryos and larvae, indicating the utility of this carrier for compound screening in zebrafish. However, given the relatively small differences (2-3 fold) between concentrations that are apparently safe and those that are clearly toxic, further studies - e.g. omics analyses -should be carried out to determine which cellular processes and signalling pathways are affected by any solvents and carriers that are used for small-molecule screens in zebrafish.
format	article
author	Jan Maes Lien Verlooy Olivia E Buenafe Peter A M de Witte Camila V Esguerra Alexander D Crawford
author_facet	Jan Maes Lien Verlooy Olivia E Buenafe Peter A M de Witte Camila V Esguerra Alexander D Crawford
author_sort	Jan Maes
title	Evaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.
title_short	Evaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.
title_full	Evaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.
title_fullStr	Evaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.
title_full_unstemmed	Evaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.
title_sort	evaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/9c751d6051ab4ecd8a668a7e0507e8fb
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Evaluation of 14 organic solvents and carriers for screening applications in zebrafish embryos and larvae.

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