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 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.
Department of Biology and CESAM, University of Aveiro, Portugal.|IDÆA-CSIC, Jordi Girona 18, 08034, Barcelona, Spain.
Melissa
M
Faria
Environmental Laboratory, US Army Engineer Research and Development Center, Vicksburg, MS, USA.|Institute for Genomics, Biocomputing &Biotechnology (IGBB), Mississippi State University, Starkville, Mississippi, USA.
Natàlia
N
Garcia-Reyero
Pathological Diagnostic Service in Fish, Universitat Autònoma de Barcelona, 08190 Bellaterra, Spain.
Francesc
F
Padrós
Rare Diseases, Genetic and Metabolism (MRGM), Université de Bordeaux, EA 4576, F-3340 Talence, France.
Patrick J
PJ
Babin
Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain.|Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain.|Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08017 Barcelona, Spain.
David
D
Sebastián
EPOC, UMR CNRS 5805, Université de Bordeaux, 33405 Talence, France;
Jérôme
J
Cachot
CID-CSIC, Jordi Girona 18, 08034, Barcelona, Spain.
Eva
E
Prats
Institute for Genomics, Biocomputing & Biotechnology (IGBB), Mississippi State University, Starkville, Mississippi, USA.
Mark
M
Arick Ii
Department of Cellular and Molecular Medicine, CIB-CSIC, Ramiro de Maetzu 9, 28040, Madrid, Spain.
Eduardo
E
Rial
Rare Diseases, Genetic and Metabolism (MRGM), Université de Bordeaux, EA 4576, F-3340 Talence, France.
Anja
A
Knoll-Gellida
Rare Diseases, Genetic and Metabolism (MRGM), Université de Bordeaux, EA 4576, F-3340 Talence, France.
Guilaine
G
Mathieu
EPOC, UMR CNRS 5805, Université de Bordeaux, 33405 Talence, France;
Florane
F
Le Bihanic
Environmental Laboratory, US Army Engineer Research and Development Center, Vicksburg, MS, USA.
B Lynn
BL
Escalon
Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain.|Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain.|Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08017 Barcelona, Spain.
Antonio
A
Zorzano
Department of Biology and CESAM, University of Aveiro, Portugal.
Amadeu M V M
AM
Soares
IDÆA-CSIC, Jordi Girona 18, 08034, Barcelona, Spain.
Demetrio
D
Raldúa
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D051337:Chemical Terrorism; D004390:Chlorpyrifos / Q000633:toxicity*; D004195:Disease Models, Animal; D006801:Humans; D062025:Organophosphate Poisoning / Q000188:drug therapy* / Q000503:physiopathology; D054852:Small Molecule Libraries / Q000008:administration & dosage* / Q000737:chemistry; D015027:Zebrafish
D054852:Small Molecule Libraries; D000110:Acetylcholinesterase; D004390:Chlorpyrifos