A comparison of the neuroprotective efficacy of newly developed oximes (K117, K127) and currently available oxime (obidoxime) in tabun-poisoned rats
Jazyk angličtina Země Anglie, Velká Británie Médium print
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
19730756
PubMed Central
PMC2736538
DOI
10.1080/15376510802455362
Knihovny.cz E-zdroje
- MeSH
- chemické bojové látky otrava MeSH
- cholinesterasové inhibitory otrava MeSH
- krysa rodu Rattus MeSH
- neuroprotektivní látky farmakologie MeSH
- organofosfáty MeSH
- otrava organofosfáty * MeSH
- oximy farmakologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- pyridinové sloučeniny farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- chemické bojové látky MeSH
- cholinesterasové inhibitory MeSH
- K117 compound MeSH Prohlížeč
- K127 compound MeSH Prohlížeč
- neuroprotektivní látky MeSH
- organofosfáty MeSH
- oximy MeSH
- pyridinové sloučeniny MeSH
- tabun MeSH Prohlížeč
The potency of newly developed bispyridinium compounds (K117, K127) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oxime (obidoxime) using functional observational battery. The neuroprotective effects of atropine alone and atropine combined with one of three bispyridinium oximes (K117, K127, obidoxime) on rats poisoned with tabun at a sublethal dose (180 microg/kg i.m.; 80% of LD(50) value) were studied. Tabun-induced neurotoxicity was monitored using a functional observational battery and automatic measurement of motor activity at 24 h following tabun challenge. The results indicated that all tested oximes combined with atropine enabled tabun-poisoned rats to survive 24 h following tabun challenge while one tabun-poisoned rats died within 24 h after tabun poisoning when the rats were treated with atropine alone. Newly developed oxime K127 combined with atropine was the most effective in decreasing tabun-induced neurotoxicity in the case of sublethal poisonings among all oximes tested. Nevertheless, the differences of neuroprotective efficacy between K127 and obidoxime are not sufficient to replace obidoxime by K127 for the treatment of acute tabun poisonings.
Department of Toxicology Faculty of Military Health Sciences Trebesska Hradec Kralove Czech Republic
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Cabal J., Bajgar J. Tabun—reappearance 50 years later (in Czech) Chem. Listy. 1999;93:27–31.
Cabal J., Kuca K., Kassa J. Specification of the structure of oximes able to reactivate tabun-inhibited acetylcholinesterase. Pharmacol. Toxicol. 2004;95:81–86. PubMed
Cassel G., Karlsson L., Waara L., Wee Ang K., Goransson-Nyberg A. Pharmacokinetics and effects of HI-6 in blood and brain of soman-intoxicated rats: a microdialysis study. Eur. J. Pharmacol. 1997;332:43–52. PubMed
Dawson R. M. Review of oximes available for treatment of nerve agent poisoning. J. Appl. Toxicol. 1994;14:317–331. PubMed
Dohnal V., Kuca K., Jun D. Prediction of a new broad-spectrum reactivator capable of reactivating acetylcholinesterase inhibited by nerve agents. J. Appl. Toxicol. 2005;3:139–145.
Ekström F., Akfur C., Tunemalm A. K., Lundberg S. Structural changes of phenylalanine 338 and histidine 447 revealed by the crystal structures of tabun-inhibited murine acetylcholinesterase. Biochemistry. 2006;45:74–81. PubMed
Frantik E., Hornychova M. Clustering of neurobehavioral measures of toxicity. Homeostasis. 1995;36:19–25.
Hornychova M., Frantik E., Kubat J., Formanek J. Neurotoxicity profile of supermethrin, a new pyrethroid insecticide. Cent. Eur. J. Publ. Health. 1995;3:210–218. PubMed
Jokanovic M. Anticholinesterase activity and delayed neurotoxic effects of tabun in hens. Vojvosanit. Pregl. 1993;50:451–456. PubMed
Jokanovic M., Maksimovic M., Kilibarda V., Jovanovic D., Savic D. Oxime-induced reactivation of acetycholinesterase inhibited by phosphoramidates. Toxicol. Lett. 1996;85:35–39. PubMed
Kassa J. Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents. J. Toxicol. Clin. Toxicol. 2002;40:803–816. PubMed
Kassa J., Karasova J. The evaluation of the neuroprotective effects of bispyridinium oximes in tabun-poisoned rats. J. Toxicol. Environ. Health A. 2007;70:1556–1567. PubMed
Kassa J., Koupilova M. The importance of anticholinergic drug selection for the neuroprotective effects of antidotes in soman-poisoned rats. Homeostasis. 2000;1–2:52–53.
Kassa J., Krejcova G. Neuroprotective effects of currently used antidotes in tabun-poisoned rats. Pharmacol. Toxicol. 2003;92:258–264. PubMed
Kassa J., Kunesova G. Comparison of the neuroprotective effects of the newly developed oximes (K027, K048) with trimedoxime in tabun-poisoned rats. J. Appl. Biomed. 2006;4:123–134.
Kassa J., Cabal J., Kuca K. A comparison of the efficacy of currently available oximes against tabun in rats. Biologia. 2005;60(Suppl. 17):77–79.
Kassa J., Karasova J., Musilek K., Kuca K., Jung Y.-S. A comparison of the therapeutic and reactivating efficacy of newly developed oximes (K117, K127) and curently avaialble oximes (obidoxime, trimedoxime, HI-6) in tabun-poisoned rats and mice. Drug Chem. Toxicol. 2008;31:371–381. PubMed
Kim T.-H., Kuca K., Jun D., Jung Y.-S. Design and synthesis of new bis-pyridinium oxime reactivators for acetylcholinesterase inhibited by organophosphorous nerve agents. Bioorg. Med. Chem. Lett. 2005;15:2914–2917. PubMed
Kuca K., Jun D., Musilek K. Structural requirements of acetylcholinesterase reactivators. Mini Rev. Med. Chem. 2006;6:269–277. PubMed
Lotti M. Organophosphorus compounds. In: Spencer P. S., Schaumburg H. H., editors. Experimental and Clinical Neurotoxicology. New York: Oxford University Press; 2000. pp. 898–925.
Marrs T. C. Organophosphate poisoning. Pharmacol. Ther. 1993;58:51–66. PubMed
McDonough J. H., Jr., Zoeffel L. D., McMonagle J., Copeland T. L., Smith C. D., Shih T.-M. Anticonvulsant treatment of nerve agent seizures: anticholinergics versus diazepam in soman-intoxicated guinea-pigs. Epilepsy Res. 2000;38:1–14. PubMed
Moser V. C., Tilson H., McPhail R. C., Becking G. C., Cuomo V., Frantik E., Kulig B. M., Winneke G. The IPCS collaborative study on neurobehavioral screening methods: II. Protocol design and testing procedures. Neurotoxicology. 1997;18:929–938. PubMed
Musilek K., Kuca K., Jun D., Dohnal V., Kim T.-H., Jung Y.-S., Dolezal M. Synthesis of reactivators of phosphorylated acetylcholinestrerase of bis-pyridiniumdialdoxime type with a 3-oxapentane connecting chain and their testing in vitro on a model of the enzyme inhibited by chlorpyrifos and methylchlorpyrifos. (in Czech) Ces. Slov. Farm. 2006;55:115–119. PubMed
Musilek K., Kuca K., Jun D., Dolezal M. Progress in synthesis of new acetylcholinesterase reactivators during the period 1990–2004. Curr. Org. Chem. 2007;11:229–238.
Ohtomi S., Takase M., Kumagai F. Sarin poisoning in Japan. A clinical experience in Japan Self Defense Force (JSDF) Central Hospital. Int. Rev. Arm. Ser. 1996;69:97–102.
Puu G., Artursson E., Bucht G. Reactivation of nerve agent inhibited acetylcholinesterase by HI-6 and obidoxime. Biochem. Pharmacol. 1986;35:1505–1510. PubMed
Roth Z., Josifko M., Maly V., Trcka V. Statistical Methods in Experimental Medicine (in Czech) Prague: SZN; 1962.
Sakurada K., Matsubara K., Shimizu K., Shiono H., Seto Y., Tsuge K., Toshibo M., Sakai I., Mukoyama H., Takatori T. Pralidoxime iodide (2-PAM) penetrates across the blood-brain barrier. Neurochem. Res. 2003;28:1401–1407. PubMed
Taylor P. Anticholinesterase agents. In: Hardman J. G., Limbird L. E., editors. The Pharmacological Basis of Therapeutics. New York: McGraw Hill; 1996. pp. 161–176.
Worek F., Widmann R., Knopff O., Szinicz L. Reactivating potency of obidoxime, pralidoxime, HI-6 and HLö-7 in human erythrocyte acetylcholinesterase inhibited by highly toxic organophosphorus compounds. Arch. Toxicol. 1998;72:237–243. PubMed