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 in: | Scientific reports Vol. 5; no. 1; pp. 15591 - 15606 |
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| Main Authors: | , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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22-10-2015
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| 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 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. |
|---|---|
| AbstractList | 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. 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. |
| ArticleNumber | 15591 |
| Author | Le Bihanic, Florane Arick, Mark Faria, Melissa Zorzano, Antonio Cachot, Jérôme Padrós, Francesc Knoll-Gellida, Anja Raldúa, Demetrio Sebastián, David Babin, Patrick J. Rial, Eduardo Escalon, B. Lynn Prats, Eva Mathieu, Guilaine Garcia-Reyero, Natàlia Soares, Amadeu M. V. M |
| Author_xml | – sequence: 1 givenname: Melissa surname: Faria fullname: Faria, Melissa organization: Department of Biology and CESAM, University of Aveiro, IDÆA-CSIC – sequence: 2 givenname: Natàlia surname: Garcia-Reyero fullname: Garcia-Reyero, Natàlia organization: Environmental Laboratory, US Army Engineer Research and Development Center, Institute for Genomics, Biocomputing & Biotechnology (IGBB), Mississippi State University – sequence: 3 givenname: Francesc surname: Padrós fullname: Padrós, Francesc organization: Pathological Diagnostic Service in Fish, Universitat Autònoma de Barcelona – sequence: 4 givenname: Patrick J. surname: Babin fullname: Babin, Patrick J. organization: Rare Diseases, Genetic and Metabolism (MRGM), Université de Bordeaux – sequence: 5 givenname: David surname: Sebastián fullname: Sebastián, David organization: Institute for Research in Biomedicine (IRB Barcelona), Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) – sequence: 6 givenname: Jérôme surname: Cachot fullname: Cachot, Jérôme organization: EPOC, UMR CNRS 5805, Université de Bordeaux – sequence: 7 givenname: Eva surname: Prats fullname: Prats, Eva organization: CID-CSIC – sequence: 8 givenname: Mark surname: Arick fullname: Arick, Mark organization: Environmental Laboratory, US Army Engineer Research and Development Center – sequence: 9 givenname: Eduardo surname: Rial fullname: Rial, Eduardo organization: Department of Cellular and Molecular Medicine – sequence: 10 givenname: Anja surname: Knoll-Gellida fullname: Knoll-Gellida, Anja organization: Rare Diseases, Genetic and Metabolism (MRGM), Université de Bordeaux – sequence: 11 givenname: Guilaine surname: Mathieu fullname: Mathieu, Guilaine organization: Rare Diseases, Genetic and Metabolism (MRGM), Université de Bordeaux – sequence: 12 givenname: Florane surname: Le Bihanic fullname: Le Bihanic, Florane organization: EPOC, UMR CNRS 5805, Université de Bordeaux – sequence: 13 givenname: B. Lynn surname: Escalon fullname: Escalon, B. Lynn organization: EPOC, UMR CNRS 5805, Université de Bordeaux – sequence: 14 givenname: Antonio surname: Zorzano fullname: Zorzano, Antonio organization: Institute for Research in Biomedicine (IRB Barcelona), Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) – sequence: 15 givenname: Amadeu M. V. M surname: Soares fullname: Soares, Amadeu M. V. M organization: Department of Biology and CESAM, University of Aveiro – sequence: 16 givenname: Demetrio surname: Raldúa fullname: Raldúa, Demetrio organization: IDÆA-CSIC |
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| Snippet | Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by... |
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| SubjectTerms | 101/28 13/51 14/34 14/63 38/91 631/154/570 64/116 692/308/1426 Acetylcholinesterase Acetylcholinesterase - metabolism Animals Armes químiques Biological & chemical weapons Calcium Chemical Terrorism Chemical weapons Chlorpyrifos Chlorpyrifos - toxicity Disease Models, Animal Glutamate receptors Humanities and Social Sciences Humans Immune response Immunosuppressive agents Inflammation Larvae Life Sciences multidisciplinary N-Methyl-D-aspartic acid receptors Nerve agents Organophosphate Poisoning - drug therapy Organophosphate Poisoning - physiopathology Pesticides Poisoning Receptor mechanisms Science Small Molecule Libraries - administration & dosage Small Molecule Libraries - chemistry Toxicologia Toxicology War Zebrafish |
| Title | Zebrafish Models for Human Acute Organophosphorus Poisoning |
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