Zebrafish Models for Human Acute Organophosphorus Poisoning

Melissa Faria, Natàlia Garcia-Reyero, Francesc Padrós, Patrick J. Babin, David Sebastián, Jérôme Cachot, Eva Prats, Mark Arick, Eduardo Rial, Anja Knoll-Gellida, Guilaine Mathieu, Florane Le Bihanic, B. Lynn Escalon, Antonio Zorzano, Amadeu M.V.M. Soares, Demetrio Ralduá

Research output: Contribution to journalArticleResearchpeer-review

42 Citations (Scopus)

Abstract

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 1990â ‰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.
Original languageEnglish
Article number15591
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 22 Oct 2015

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