Carbamate nerve agent prophylatics exhibit distinct toxicological effects in the zebrafish embryo model

Fischer, Audrey; Wolman, Marc A.; Granato, Michael; Parsons, Michael; McCallion, Andrew S.; Proescher, Jody B.; English, Emily

doi:10.1016/j.ntt.2015.05.001

Cited by 13 publications

(13 citation statements)

References 58 publications

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“…It is interesting to note that another study investigating the effects of subacute exposure to carbamate compounds, such as pyridostigmine bromide, that temporarily inhibit AChE produced similar gross morphological changes to the OP pesticides but required a 1000-fold higher concentration. 49 Exposure to chlorpyrifos at the sublethal concentration of 10 M at 1-3 dpf produced kyphosis and a decrease in heart rate, while exposure to 100 M diazinon induced cardiac edema and decreased blood flow. 39 Malathion exposure at a Exposures were conducted for the indicated time, and mortality was recorded at 24 h as indicated by cessation of heartbeat.…”

Section: Op Pesticide-induced Developmental Toxicity and Behavioral Dmentioning

confidence: 99%

“…It suggests that a critical level of AChE activity must be maintained during development to maintain normal neuronal morphology. It is interesting to note that another study investigating the effects of subacute exposure to carbamate compounds, such as pyridostigmine bromide, that temporarily inhibit AChE produced similar gross morphological changes to the OP pesticides but required a 1000‐fold higher concentration …”

Section: Op Pesticide–induced Developmental Toxicity and Behavioral Dmentioning

confidence: 99%

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Zebrafish as a model for acetylcholinesterase‐inhibiting organophosphorus agent exposure and oxime reactivation

Koenig

Dao

Kan

et al. 2016

Annals of the New York Academy of Sciences

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The current research progression efforts for investigating novel treatments for exposure to organophosphorus (OP) compounds that inhibit acetylcholinesterase (AChE), including pesticides and chemical warfare nerve agents (CWNAs), rely solely on in vitro cell assays and in vivo rodent models. The zebrafish (Danio rerio) is a popular, well-established vertebrate model in biomedical research that offers high-throughput capabilities and genetic manipulation not readily available with rodents. A number of research studies have investigated the effects of subacute developmental exposure to OP pesticides in zebrafish, observing detrimental effects on gross morphology, neuronal development, and behavior. Few studies, however, have utilized this model to evaluate treatments, such as oxime reactivators, anticholinergics, or anticonvulsants, following acute exposure. Preliminary work has investigated the effects of CWNA exposure. The results clearly demonstrated relative toxicity and oxime efficacy similar to that reported for the rodent model. This review surveys the current literature utilizing zebrafish as a model for OP exposure and highlights its potential use as a high-throughput system for evaluating AChE reactivator antidotal treatments to acute pesticide and CWNA exposure.

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Section: Op Pesticide-induced Developmental Toxicity and Behavioral Dmentioning

confidence: 99%

Section: Op Pesticide–induced Developmental Toxicity and Behavioral Dmentioning

confidence: 99%

Zebrafish as a model for acetylcholinesterase‐inhibiting organophosphorus agent exposure and oxime reactivation

Koenig

Dao

Kan

et al. 2016

Annals of the New York Academy of Sciences

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“…AChE activity is affianced as neurotoxicity biomarker (Rose et al, 2016). The altered patterns of neuronal connectivity contributed to the developmental neurotoxicity of carbamates and demonstrated the utility of the zebra fish model for distinguishing subtle structure-based differential effects of AChE inhibitors, which include nerve agents (Fischer et al, 2015). Barbieri et al, (2016) have reported that these effects can result in metabolic disorders which are reflected in changes in oxygen consumption and ammonia excretion.…”

Section: Discussionmentioning

confidence: 99%

Acute toxicity and residue analysis of cartap hydrochloride pesticide: Toxicological implications on the fingerlings of fresh water fish Labeo rohita

Ch.

Veeraiah

Padmavathi

et al. 2016

Biocatalysis and Agricultural Biotechnology

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“…The final concentration of the solvent in the exposure solutions was 0.01 %, except for the reversible AChE inhibitors. Several of these compounds only weakly penetrate the skin of zebrafish larvae in water (Behra et al 2004; Fischer et al 2015); thus, 1 % DMSO was added to the exposure medium for this group of compounds (Berghmans et al 2008). A preliminary range-finding test was performed for each drug, and the final selected concentration corresponds to the no observed effect concentration (NOEC) for survival and gross morphological defects, unless otherwise stated.…”

Section: Methodsmentioning

confidence: 99%

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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Carbamate nerve agent prophylatics exhibit distinct toxicological effects in the zebrafish embryo model

Cited by 13 publications

References 58 publications

Zebrafish as a model for acetylcholinesterase‐inhibiting organophosphorus agent exposure and oxime reactivation

Zebrafish as a model for acetylcholinesterase‐inhibiting organophosphorus agent exposure and oxime reactivation

Acute toxicity and residue analysis of cartap hydrochloride pesticide: Toxicological implications on the fingerlings of fresh water fish Labeo rohita

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

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