TY - JOUR
T1 - Zebrafish Models for Human Acute Organophosphorus Poisoning
AU - Faria, Melissa
AU - Garcia-Reyero, Natàlia
AU - Padrós, Francesc
AU - Babin, Patrick J.
AU - Sebastián, David
AU - Cachot, Jérôme
AU - Prats, Eva
AU - Arick, Mark
AU - Rial, Eduardo
AU - Knoll-Gellida, Anja
AU - Mathieu, Guilaine
AU - Le Bihanic, Florane
AU - Escalon, B. Lynn
AU - Zorzano, Antonio
AU - Soares, Amadeu M.V.M.
AU - Ralduá, Demetrio
PY - 2015/10/22
Y1 - 2015/10/22
N2 - 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.
AB - 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.
U2 - 10.1038/srep15591
DO - 10.1038/srep15591
M3 - Article
VL - 5
M1 - 15591
ER -