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Oximes as pretreatment before acute exposure to paraoxon
DE. Lorke, SM. Nurulain, MY. Hasan, K. Kuča, GA. Petroianu,
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Science - International
PubMed
31264735
DOI
10.1002/jat.3835
Knihovny.cz E-zdroje
- MeSH
- analýza přežití MeSH
- LD50 MeSH
- obidoxim chlorid aplikace a dávkování farmakologie MeSH
- ochranné látky aplikace a dávkování farmakologie MeSH
- paraoxon chemie toxicita MeSH
- potkani Wistar MeSH
- pralidoximové sloučeniny aplikace a dávkování farmakologie MeSH
- proporcionální rizikové modely MeSH
- reaktivátory cholinesterasy aplikace a dávkování farmakologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Organophosphates, useful agents as pesticides, also represent a serious danger due to their high acute toxicity. There is indication that oximes, when administered before organophosphate exposure, can protect from these toxic effects. We have tested at equitoxic dosage (25% of LD01 ) the prophylactic efficacy of five experimental (K-48, K-53, K-74, K-75, K-203) and two established oximes (pralidoxime and obidoxime) to protect from mortality induced by the organophosphate paraoxon. Mortalities were quantified by Cox analysis and compared with those observed after pretreatment with a strong acetylcholinesterase inhibitor (10-methylacridine) and after the FDA-approved pretreatment compound pyridostigmine. All nine tested substances statistically significantly reduced paraoxon-induced mortality. Best protection was conferred by the experimental oxime K-48, reducing the relative risk of death (RR) to 0.10, which was statistically significantly superior to pyridostigmine (RR = 0.31). The other oximes reduced the RR to 0.13 (obidoxime), 0.20 (K-203), 0.21 (K-74), 0.24 (K-75) and 0.26 (pralidoxime), which were significantly more efficacious than 10-methylacridine (RR = 0.65). These data support the hypothesis that protective efficacy is not primarily due to cholinesterase inhibition and indicate that the tested experimental oximes may be considered promising alternatives to the established pretreatment compound pyridostigmine.
Citace poskytuje Crossref.org
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- $a Lorke, Dietrich E $u Department of Cellular Biology & Pharmacology, Herbert Wertheim College of Medicine, University Park GL 495 D, Florida International University, Miami, Florida. College of Medicine and Health Sciences, Department of Anatomy and Cellular Biology, Khalifa University, Abu Dhabi, United Arab Emirates.
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- $a Organophosphates, useful agents as pesticides, also represent a serious danger due to their high acute toxicity. There is indication that oximes, when administered before organophosphate exposure, can protect from these toxic effects. We have tested at equitoxic dosage (25% of LD01 ) the prophylactic efficacy of five experimental (K-48, K-53, K-74, K-75, K-203) and two established oximes (pralidoxime and obidoxime) to protect from mortality induced by the organophosphate paraoxon. Mortalities were quantified by Cox analysis and compared with those observed after pretreatment with a strong acetylcholinesterase inhibitor (10-methylacridine) and after the FDA-approved pretreatment compound pyridostigmine. All nine tested substances statistically significantly reduced paraoxon-induced mortality. Best protection was conferred by the experimental oxime K-48, reducing the relative risk of death (RR) to 0.10, which was statistically significantly superior to pyridostigmine (RR = 0.31). The other oximes reduced the RR to 0.13 (obidoxime), 0.20 (K-203), 0.21 (K-74), 0.24 (K-75) and 0.26 (pralidoxime), which were significantly more efficacious than 10-methylacridine (RR = 0.65). These data support the hypothesis that protective efficacy is not primarily due to cholinesterase inhibition and indicate that the tested experimental oximes may be considered promising alternatives to the established pretreatment compound pyridostigmine.
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- $a Nurulain, Syed M $u Department of Bio Science, COMSATS Institute of Information Technology, Islamabad, Pakistan.
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