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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Published inScientific reports
Main Authors Faria, Melissa, Garcia-Reyero, Natàlia, Padrós, Francesc, Babin, Patrick J, Sebastián Muñoz, David, Cachot, Jérôme, Prats, Eva, Arick II, Mark, Rial, Eduardo, Knoll-Gellida, Anja, Mathieu, Guilaine, Le Bihanic, Florane, Escalon, B. Lynn, Zorzano Olarte, Antonio, Soares, Amadeu M.V.M, Raldúa, Demetrio
Format Journal Article
LanguageEnglish
Published Nature Publishing Group 22.10.2015
Subjects
Armes químiques
Chemical weapons
Toxicologia
Toxicology
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Summary: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.
ISSN:2045-2322
2045-2322