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Article

Development of a Larval Zebrafish Model for Acute Organophosphorus Nerve Agent and Pesticide Exposure and Therapeutic Evaluation

Medical Toxicology Research Division, Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA
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Toxics 2020, 8(4), 106; https://doi.org/10.3390/toxics8040106
Received: 10 October 2020 / Revised: 30 October 2020 / Accepted: 12 November 2020 / Published: 17 November 2020
(This article belongs to the Special Issue Advanced Zebrafish Model for Environmental Health Sciences Research)
Organophosphorus compound exposure remains a present threat through agricultural accidents, warfare, or terrorist activity. The primary mechanism of organophosphorus toxicity is through inhibition of the enzyme acetylcholinesterase, with current emergency treatment including anticholinergics, benzodiazepines, and oxime reactivators. However, a need for more effective and broadly acting countermeasures remains. This study aimed to develop larval zebrafish as a high-throughput model for evaluating novel therapeutics against acute organophosphorus exposure. Larval zebrafish at six days post-fertilization were exposed to acute concentrations of seven organophosphorus compounds and treated with one of three oximes. Lethality studies indicated similar relative toxicity to that seen in the established rodent model, with chemical warfare agents proving more lethal than organophosphorus pesticides. Additionally, the organophosphorus-specific response for oxime reactivation of acetylcholinesterase was comparable to what has been previously reported. Behavioral studies measuring the visual motor response demonstrated greater efficacy for centrally acting oxime compounds than for those that are contained to the peripheral tissue. Overall, these results support the use of this larval zebrafish model as a high-throughput screening platform for evaluating novel treatments following acute organophosphorus exposure. View Full-Text
Keywords: acetylcholinesterase; cholinesterase inhibitor; organophosphorus compound; oxime reactivator; zebrafish acetylcholinesterase; cholinesterase inhibitor; organophosphorus compound; oxime reactivator; zebrafish
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MDPI and ACS Style

Koenig, J.A.; Acon Chen, C.; Shih, T.-M. Development of a Larval Zebrafish Model for Acute Organophosphorus Nerve Agent and Pesticide Exposure and Therapeutic Evaluation. Toxics 2020, 8, 106. https://doi.org/10.3390/toxics8040106

AMA Style

Koenig JA, Acon Chen C, Shih T-M. Development of a Larval Zebrafish Model for Acute Organophosphorus Nerve Agent and Pesticide Exposure and Therapeutic Evaluation. Toxics. 2020; 8(4):106. https://doi.org/10.3390/toxics8040106

Chicago/Turabian Style

Koenig, Jeffrey A., Cindy Acon Chen, and Tsung-Ming Shih. 2020. "Development of a Larval Zebrafish Model for Acute Organophosphorus Nerve Agent and Pesticide Exposure and Therapeutic Evaluation" Toxics 8, no. 4: 106. https://doi.org/10.3390/toxics8040106

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