ArticleJournal of biomolecular screening2013
An in vivo zebrafish screen identifies organophosphate antidotes with diverse mechanisms of action.
Article in Journal of biomolecular screening, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Review
- Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplastics.Frontiers in toxicology · 2025Review
- An assessment of vaping-induced inflammation and toxicity: A feasibility study using a 2-stage zebrafish and mouse platform.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- Article
- Biochemical responses of a freshwater fish Cirrhinus mrigala exposed to tris(2-chloroethyl) phosphate (TCEP).Environmental science and pollution research international · 2020Article
- An Appraisal of Antidotes' Effectiveness: Evidence of the Use of Phyto-Antidotes and Biotechnological Advancements.Molecules (Basel, Switzerland) · 2020Review
- Application of the Transcriptional Disease Signature (TDSs) to Screen Melanoma-Effective Compounds in a Small Fish Model.Scientific reports · 2019Article
- How Surrogate and Chemical Genetics in Model Organisms Can Suggest Therapies for Human Genetic Diseases.Genetics · 2018Review
- Resorcinol-, catechol- and saligenin-based bronchodilating β2-agonists as inhibitors of human cholinesterase activity.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Utilizing Zebrafish Visual Behaviors in Drug Screening for Retinal Degeneration.International journal of molecular sciences · 2017Review
- Chemical screening in zebrafish for novel biological and therapeutic discovery.Methods in cell biology · 2017Review
- Zebrafish as a model for acetylcholinesterase-inhibiting organophosphorus agent exposure and oxime reactivation.Annals of the New York Academy of Sciences · 2016Review
- Determination of dichlorvos residue levels in vegetables sold in Lusaka, Zambia.The Pan African medical journal · 2016Article
- Zebrafish as tools for drug discovery.Nature reviews. Drug discovery · 2015Review
- 15 years of zebrafish chemical screening.Current opinion in chemical biology · 2015Article
- Developing highER-throughput zebrafish screens for in-vivo CNS drug discovery.Frontiers in behavioral neuroscience · 2015Article
- Changing the Scale and Efficiency of Chemical Warfare Countermeasure Discovery Using the Zebrafish.Drug discovery today. Disease models · 2013Article
- A zebrafish model of hyperammonemia.Molecular genetics and metabolismArticle
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a high priority. Early life stage zebrafish exposed to organophosphates exhibit several phenotypes that parallel the human response to organophosphates, including behavioral deficits, paralysis, and eventual death. Here, we have developed a high-throughput zebrafish screen in a 96-well plate format to find new antidotes that counteract organophosphate-induced lethality. In a pilot screen of 1200 known drugs, we identified 16 compounds that suppress organophosphate toxicity in zebrafish. Several in vitro assays coupled with liquid chromatography/tandem mass spectrometry-based metabolite profiling enabled determination of mechanisms of action for several of the antidotes, including reversible acetylcholinesterase inhibition, cholinergic receptor antagonism, and inhibition of bioactivation. Therefore, the in vivo screen is capable of discovering organophosphate antidotes that intervene in distinct pathways. These findings suggest that zebrafish screens might be a broadly applicable approach for discovering compounds that counteract the toxic effects of accidental or malicious poisonous exposures.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.