Zebrafish Models for Human Acute Organophosphorus Poisoning

Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeas...

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Main Authors:	Faria, Melissa, Garcia-Reyero, Natàlia, Padrós, Francesc, Babin, Patrick J., Sebastián, David, Cachot, Jérôme, Prats, Eva, Arick II, Mark, Rial, Eduardo, Knoll-Gellida, Anja, Mathieu, Guilaine, Le Bihanic, Florane, Escalon, B. Lynn, Zorzano, Antonio, Soares, Amadeu M.V.M, Raldúa, Demetrio
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614985/

id	pubmed-4614985
recordtype	oai_dc
spelling	pubmed-46149852015-10-29 Zebrafish Models for Human Acute Organophosphorus Poisoning Faria, Melissa Garcia-Reyero, Natàlia Padrós, Francesc Babin, Patrick J. Sebastián, David Cachot, Jérôme Prats, Eva Arick II, Mark Rial, Eduardo Knoll-Gellida, Anja Mathieu, Guilaine Le Bihanic, Florane Escalon, B. Lynn Zorzano, Antonio Soares, Amadeu M.V.M Raldúa, Demetrio Article Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning. Nature Publishing Group 2015-10-22 /pmc/articles/PMC4614985/ /pubmed/26489395 http://dx.doi.org/10.1038/srep15591 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Faria, Melissa Garcia-Reyero, Natàlia Padrós, Francesc Babin, Patrick J. Sebastián, David Cachot, Jérôme Prats, Eva Arick II, Mark Rial, Eduardo Knoll-Gellida, Anja Mathieu, Guilaine Le Bihanic, Florane Escalon, B. Lynn Zorzano, Antonio Soares, Amadeu M.V.M Raldúa, Demetrio
spellingShingle	Faria, Melissa Garcia-Reyero, Natàlia Padrós, Francesc Babin, Patrick J. Sebastián, David Cachot, Jérôme Prats, Eva Arick II, Mark Rial, Eduardo Knoll-Gellida, Anja Mathieu, Guilaine Le Bihanic, Florane Escalon, B. Lynn Zorzano, Antonio Soares, Amadeu M.V.M Raldúa, Demetrio Zebrafish Models for Human Acute Organophosphorus Poisoning
author_facet	Faria, Melissa Garcia-Reyero, Natàlia Padrós, Francesc Babin, Patrick J. Sebastián, David Cachot, Jérôme Prats, Eva Arick II, Mark Rial, Eduardo Knoll-Gellida, Anja Mathieu, Guilaine Le Bihanic, Florane Escalon, B. Lynn Zorzano, Antonio Soares, Amadeu M.V.M Raldúa, Demetrio
author_sort	Faria, Melissa
title	Zebrafish Models for Human Acute Organophosphorus Poisoning
title_short	Zebrafish Models for Human Acute Organophosphorus Poisoning
title_full	Zebrafish Models for Human Acute Organophosphorus Poisoning
title_fullStr	Zebrafish Models for Human Acute Organophosphorus Poisoning
title_full_unstemmed	Zebrafish Models for Human Acute Organophosphorus Poisoning
title_sort	zebrafish models for human acute organophosphorus poisoning
description	Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614985/
_version_	1613491033443663872

Zebrafish Models for Human Acute Organophosphorus Poisoning

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