Strategies to Enhance Medical Countermeasures After the Use of Chemical Warfare Agents on Civilians

Jett, David A.; Yeung, David T.

doi:10.1016/b978-0-12-800159-2.00070-1

Cited by 2 publications

(3 citation statements)

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“…In developing countries, in particular those from the Asia–Pacific region, the major concern is self-poisoning with OP pesticides. However, developed countries are predominantly concerned with the potential use of highly toxic OP compounds by terrorists or the release of these compounds during transportation or from storage facilities after an accident or natural disaster (Jett and Yeung 2015). …”

Section: Introductionmentioning

confidence: 99%

“…Pyridostigmine bromide is the only FDA-approved prophylactic drug (Jett and Yeung 2015), and standard therapy is essentially restricted to the administration of atropine to counteract muscarinic overstimulation and an oxime to reactivate AChE (Balali-Mood and Saber 2012). Administration of benzodiazepines to control convulsions and mechanical respiration may be required.…”

Section: Introductionmentioning

confidence: 99%

“…First, a pre - treatment therapeutic approach was designed to assess the suitability of the zebrafish model for identifying medical countermeasures that protect against intoxication when administered prior to acute OP exposure. Personnel that should be pre-treated with these medical countermeasures include first responders, such as emergency medical technicians, and individuals responsible for site decontamination (Jett and Yeung 2015). Four reversible AChE inhibitors (huperzine A, galantamine, physostigmine and pyridostigmine), as well as the muscarinic AChR antagonist atropine and the oxime pralidoxime, were tested using the pre-treatment approach.…”

Section: Introductionmentioning

confidence: 99%

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Zebrafish is a predictive model for identifying compounds that protect against brain toxicity in severe acute organophosphorus intoxication

et al. 2016

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Acute organophosphorus (OP) intoxication is a worldwide clinical and public health problem. In addition to cholinergic crisis, neurodegeneration and brain damage are hallmarks of the severe form of this toxidrome. Recently, we generated a chemical model of severe acute OP intoxication in zebrafish that is characterized by altered head morphology and brain degeneration. The pathophysiological pathways resulting in brain toxicity in this model are similar to those described in humans. The aim of this study was to assess the predictive power of this zebrafish model by testing the effect of a panel of drugs that provide protection in mammalian models. The selected drugs included “standard therapy” drugs (atropine and pralidoxime), reversible acetylcholinesterase inhibitors (huperzine A, galantamine, physostigmine and pyridostigmine), N-methyl-d-aspartate (NMDA) receptor antagonists (MK-801 and memantine), dual-function NMDA receptor and acetylcholine receptor antagonists (caramiphen and benactyzine) and anti-inflammatory drugs (dexamethasone and ibuprofen). The effects of these drugs on zebrafish survival and the prevalence of abnormal head morphology in the larvae exposed to 4 µM chlorpyrifos oxon [1 × median lethal concentration (LC50)] were determined. Moreover, the neuroprotective effects of pralidoxime, memantine, caramiphen and dexamethasone at the gross morphological level were confirmed by histopathological and transcriptional analyses. Our results demonstrated that the zebrafish model for severe acute OP intoxication has a high predictive value and can be used to identify new compounds that provide neuroprotection against severe acute OP intoxication.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-016-1851-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Zebrafish is a predictive model for identifying compounds that protect against brain toxicity in severe acute organophosphorus intoxication

et al. 2016

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Zebrafish Models for Human Acute Organophosphorus Poisoning

Faria

García-Reyero

Padrós

et al. 2015

Sci Rep

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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.

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Strategies to Enhance Medical Countermeasures After the Use of Chemical Warfare Agents on Civilians

Cited by 2 publications

References 26 publications

Zebrafish is a predictive model for identifying compounds that protect against brain toxicity in severe acute organophosphorus intoxication

Zebrafish is a predictive model for identifying compounds that protect against brain toxicity in severe acute organophosphorus intoxication

Zebrafish Models for Human Acute Organophosphorus Poisoning

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