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Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl

Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have asse...

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Autores principales: Lorke, Dietrich E., Nurulain, Syed M., Hasan, Mohamed Y., Kuča, Kamil, Petroianu, Georg A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002820/
https://www.ncbi.nlm.nih.gov/pubmed/33802843
http://dx.doi.org/10.3390/ijms22063072
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author Lorke, Dietrich E.
Nurulain, Syed M.
Hasan, Mohamed Y.
Kuča, Kamil
Petroianu, Georg A.
author_facet Lorke, Dietrich E.
Nurulain, Syed M.
Hasan, Mohamed Y.
Kuča, Kamil
Petroianu, Georg A.
author_sort Lorke, Dietrich E.
collection PubMed
description Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD(01), are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use.
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spelling pubmed-80028202021-03-28 Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl Lorke, Dietrich E. Nurulain, Syed M. Hasan, Mohamed Y. Kuča, Kamil Petroianu, Georg A. Int J Mol Sci Article Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD(01), are able to reduce mortality induced by the OPC azinphos-methyl. Their efficacy was compared with that of pyridostigmine, the only FDA-approved substance for such prophylaxis. Efficacy was quantified in rats by Cox analysis, calculating the relative risk of death (RR), with RR=1 for the reference group given only azinphos-methyl, but no prophylaxis. All tested compounds significantly (p ≤ 0.05) reduced azinphos-methyl-induced mortality. In addition, the efficacy of all tested experimental and established oximes except K-53 was significantly superior to the FDA-approved compound pyridostigmine. Best protection was observed for the oximes K-48 (RR = 0.20), K-27 (RR = 0.23), and obidoxime (RR = 0.21), which were significantly more efficacious than pralidoxime and pyridostigmine. The second-best group of prophylactic compounds consisted of K-74 (RR = 0.26), K-75 (RR = 0.35) and pralidoxime (RR = 0.37), which were significantly more efficacious than pyridostigmine. Pretreatment with K-53 (RR = 0.37) and pyridostigmine (RR = 0.52) was the least efficacious. Our present data, together with previous results on other OPCs, indicate that the experimental oximes K-27 and K-48 are very promising pretreatment compounds. When penetration into the brain is undesirable, obidoxime is the most efficacious prophylactic agent already approved for clinical use. MDPI 2021-03-17 /pmc/articles/PMC8002820/ /pubmed/33802843 http://dx.doi.org/10.3390/ijms22063072 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lorke, Dietrich E.
Nurulain, Syed M.
Hasan, Mohamed Y.
Kuča, Kamil
Petroianu, Georg A.
Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl
title Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl
title_full Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl
title_fullStr Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl
title_full_unstemmed Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl
title_short Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl
title_sort experimental and established oximes as pretreatment before acute exposure to azinphos-methyl
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002820/
https://www.ncbi.nlm.nih.gov/pubmed/33802843
http://dx.doi.org/10.3390/ijms22063072
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