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 Ii, Eduardo Rial, Anja Knoll-Gellida, Guilaine Mathieu, Florane Le Bihanic, B Lynn Escalon, Antonio Zorzano, Amadeu M V M Soares, Demetrio Raldúa
Author Information
Melissa Faria: Department of Biology and CESAM, University of Aveiro, Portugal.
Natàlia Garcia-Reyero: Environmental Laboratory, US Army Engineer Research and Development Center, Vicksburg, MS, USA.
Francesc Padrós: Pathological Diagnostic Service in Fish, Universitat Autònoma de Barcelona, 08190 Bellaterra, Spain.
Patrick J Babin: Rare Diseases, Genetic and Metabolism (MRGM), Université de Bordeaux, EA 4576, F-3340 Talence, France.
David Sebastián: Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain.
Jérôme Cachot: EPOC, UMR CNRS 5805, Université de Bordeaux, 33405 Talence, France;
Eva Prats: CID-CSIC, Jordi Girona 18, 08034, Barcelona, Spain.
Mark Arick Ii: Institute for Genomics, Biocomputing & Biotechnology (IGBB), Mississippi State University, Starkville, Mississippi, USA.
Eduardo Rial: Department of Cellular and Molecular Medicine, CIB-CSIC, Ramiro de Maetzu 9, 28040, Madrid, Spain.
Anja Knoll-Gellida: Rare Diseases, Genetic and Metabolism (MRGM), Université de Bordeaux, EA 4576, F-3340 Talence, France.
Guilaine Mathieu: Rare Diseases, Genetic and Metabolism (MRGM), Université de Bordeaux, EA 4576, F-3340 Talence, France.
Florane Le Bihanic: EPOC, UMR CNRS 5805, Université de Bordeaux, 33405 Talence, France;
B Lynn Escalon: Environmental Laboratory, US Army Engineer Research and Development Center, Vicksburg, MS, USA.
Antonio Zorzano: Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain.
Amadeu M V M Soares: Department of Biology and CESAM, University of Aveiro, Portugal.
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.
