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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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| author | Dietrich E. Lorke Syed M. Nurulain Mohamed Y. Hasan Kamil Kuča Georg A. Petroianu |
| author_facet | Dietrich E. Lorke Syed M. Nurulain Mohamed Y. Hasan Kamil Kuča Georg A. Petroianu |
| author_sort | Dietrich E. Lorke |
| collection | DOAJ |
| 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<sub>01</sub>, 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 (<i>p</i> ≤ 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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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:09:33Z |
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| spelling | doaj.art-433595bcea1946ff9d7f44c4f1176e562023-11-21T10:51:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01226307210.3390/ijms22063072Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-MethylDietrich E. Lorke0Syed M. Nurulain1Mohamed Y. Hasan2Kamil Kuča3Georg A. Petroianu4Department of Anatomy and Cellular Biology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab EmiratesBio Science Department, COMSATS Institute of Information Technology, Bio Sciences Block, CUI, Park Road, Tarlai Kalan, Islamabad 45550, PakistanDepartment of Pharmacology & Therapeutics, College of Medicine and Health Sciences, UAE University, Al Ain P.O. Box 15551, United Arab EmiratesDepartment of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanského 62/26, 500 03 Hradec Kralove, Czech RepublicDepartment of Pharmacology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab EmiratesPoisoning 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<sub>01</sub>, 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 (<i>p</i> ≤ 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.https://www.mdpi.com/1422-0067/22/6/3072acetylcholineazinphos-methylcarbamatescholinesteraseCox analysisobidoxime |
| spellingShingle | Dietrich E. Lorke Syed M. Nurulain Mohamed Y. Hasan Kamil Kuča Georg A. Petroianu Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl International Journal of Molecular Sciences acetylcholine azinphos-methyl carbamates cholinesterase Cox analysis obidoxime |
| 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 | acetylcholine azinphos-methyl carbamates cholinesterase Cox analysis obidoxime |
| url | https://www.mdpi.com/1422-0067/22/6/3072 |
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