Dataset Information

Diisopropylfluorophosphate (DFP) volatizes and cross-contaminates wells in a common 96-well plate format used in zebrafish larvae toxicology studies.

ABSTRACT: Diisopropylfluorophosphate (DFP) is an organophosphate (OP) that is commonly used as a surrogate of OP nerve agents to study the neurotoxic effects of acute OP intoxication. In preliminary studies, we discovered abnormally high incidence of deaths in DMSO control zebrafish larvae housed in the same 96-well plate as DFP-exposed larvae and hypothesized that DFP volatilizes and cross-contaminates wells when using static waterborne exposures. Survivability and acetylcholinesterase activity assays were indicative of the presence of DFP in the tissues of zebrafish ostensibly exposed to DMSO only. These findings are consistent with DFP cross-contamination, which raises concerns for the experimental design of studies evaluating the toxicity of volatile and semi-volatile substances in zebrafish using medium-to-high throughput approaches.

SUBMITTER: Mundy PC

PROVIDER: S-EPMC9356770 | biostudies-literature | 2022 May-Jun

REPOSITORIES: biostudies-literature

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Diisopropylfluorophosphate (DFP) volatizes and cross-contaminates wells in a common 96-well plate format used in zebrafish larvae toxicology studies.

Mundy Paige C PC Mendieta Rosalia R Lein Pamela J PJ

Journal of pharmacological and toxicological methods 20220508

Diisopropylfluorophosphate (DFP) is an organophosphate (OP) that is commonly used as a surrogate of OP nerve agents to study the neurotoxic effects of acute OP intoxication. In preliminary studies, we discovered abnormally high incidence of deaths in DMSO control zebrafish larvae housed in the same 96-well plate as DFP-exposed larvae and hypothesized that DFP volatilizes and cross-contaminates wells when using static waterborne exposures. Survivability and acetylcholinesterase activity assays we ...[more]

PMID: 35545188

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Project description:Preclinical efforts to improve medical countermeasures against organophosphate (OP) chemical threat agents have largely focused on adult male models. However, age and sex have been shown to influence the neurotoxicity of repeated low-level OP exposure. Therefore, to determine the influence of sex and age on outcomes associated with acute OP intoxication, postnatal day 28 Sprague-Dawley male and female rats were exposed to the OP diisopropylfluorophosphate (DFP; 3.4 mg/kg, s.c.) or an equal volume of vehicle (∼80 µL saline, s.c.) followed by atropine sulfate (0.1 mg/kg, i.m.) and pralidoxime (2-PAM; 25 mg/kg, i.m.). Seizure activity was assessed during the first 4 h post-exposure using behavioral criteria and electroencephalographic (EEG) recordings. At 1 d post-exposure, acetylcholinesterase (AChE) activity was measured in cortical tissue, and at 1, 7, and 28 d post-exposure, brains were collected for neuropathologic analyses. At 1 month post-DFP, animals were analyzed for motor ability, learning and memory, and hippocampal neurogenesis. Acute DFP intoxication triggered more severe seizure behavior in males than females, which was supported by EEG recordings. DFP caused significant neurodegeneration and persistent microglial activation in numerous brain regions of both sexes, but astrogliosis occurred earlier and was more severe in males compared to females. DFP males and females exhibited pronounced memory deficits relative to sex-matched controls. In contrast, acute DFP intoxication altered hippocampal neurogenesis in males, but not females. These findings demonstrate that acute DFP intoxication triggers seizures in juvenile rats of both sexes, but the seizure severity varies by sex. Some, but not all, chronic neurotoxic outcomes also varied by sex. The spatiotemporal patterns of neurological damage suggest that microglial activation may be a more important factor than astrogliosis or altered neurogenesis in the pathogenesis of cognitive deficits in juvenile rats acutely intoxicated with OPs.

Dataset Information

Diisopropylfluorophosphate (DFP) volatizes and cross-contaminates wells in a common 96-well plate format used in zebrafish larvae toxicology studies.

Publications

Diisopropylfluorophosphate (DFP) volatizes and cross-contaminates wells in a common 96-well plate format used in zebrafish larvae toxicology studies.

Similar Datasets

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