ArticleToxicology2014
Use of OpdA, an organophosphorus (OP) hydrolase, prevents lethality in an African green monkey model of acute OP poisoning.
Article in Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 17 citations in OpenAlex.
- Enhancing organophosphate hydrolase efficacy via protein engineering and immobilization strategies.Annals of the New York Academy of Sciences · 2020Review
- Efficacy of an organophosphorus hydrolase enzyme (OpdA) in human serum and minipig models of organophosphorus insecticide poisoning.Clinical toxicology (Philadelphia, Pa.) · 2020Article
- Structure Dependent Determination of Organophosphate Targets in Mammalian Tissues Using Activity-Based Protein Profiling.Chemical research in toxicology · 2020Article
- Enzymatic Bioremediation of Organophosphate Compounds-Progress and Remaining Challenges.Frontiers in bioengineering and biotechnology · 2019Review
- Organophosphate-Hydrolyzing Enzymes as First-Line of Defence Against Nerve Agent-Poisoning: Perspectives and the Road Ahead.The protein journal · 2016Review
- In vitro evaluation of the catalytic activity of paraoxonases and phosphotriesterases predicts the enzyme circulatory levels required for in vivo protection against organophosphate intoxications.Chemico-biological interactions · 2016Article
- Chronic administration of isocarbophos induces vascular cognitive impairment in rats.Journal of cellular and molecular medicine · 2016Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Organophosphorus (OP) pesticides are a diverse class of acetylcholinesterase (AChE) inhibitors that are responsible for tremendous morbidity and mortality worldwide, killing approximately 300,000 people annually. Enzymatic hydrolysis of OPs is a potential therapy for acute poisoning. OpdA, an OP hydrolase isolated from Agrobacterium radiobacter, has been shown to decrease lethality in rodent models of OP poisoning. This study investigated the effects of OpdA on AChE activity, plasma concentrations of OP, and signs of toxicity after administration of dichlorvos to nonhuman primates. A dose of 75 mg/kg dichlorvos given orally caused apnea within 10 min with a progressive decrease in heart rate. Blood AChE activity decreased to zero within 10 min. Respirations and AChE activity did not recover. The mean dichlorvos concentration rose to a peak of 0.66 μg/ml. Treated monkeys received 1.2mg/kg OpdA iv immediately after poisoning with dichlorvos. In Opda-treated animals, heart and respiratory rates were unchanged from baseline over a 240-minute observation period. AChE activity slowly declined, but remained above 25% of baseline for the entire duration. Dichlorvos concentrations reached a mean peak of 0.19 μg/ml at 40 min after poisoning and decreased to a mean of 0.05 μg/ml at 240 min. These results show that OpdA hydrolyzes dichlorvos in an African green monkey model of lethal poisoning, delays AChE inhibition, and prevents lethality.
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