Zebrafish Models for Human Acute Organophosphorus Poisoning

• Published in: Scientific reports Vol. 5; no. 1; pp. 15591 - 15606
• Main Authors: Faria, Melissa, Garcia-Reyero, Natàlia, Padrós, Francesc, Babin, Patrick J., Sebastián, David, Cachot, Jérôme, Prats, Eva, Arick, Mark, Rial, Eduardo, Knoll-Gellida, Anja, Mathieu, Guilaine, Le Bihanic, Florane, Escalon, B. Lynn, Zorzano, Antonio, Soares, Amadeu M. V. M, Raldúa, Demetrio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-10-2015; Nature Publishing Group
• Subjects: 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
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep15591

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.