J Appl Biomed 9:35-41, 2011 | DOI: 10.2478/v10136-009-0030-8

Inhibition of blood and tissue cholinesterases by soman in guinea pigs in vivo

Jiří Bajgar1,*, Jiří Kassa1, Miroslav Pohanka2, Jana ®ďárová Karasová1, Ladislav Novotný3, Josef Fusek1, Václav Bláha4
1 Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
2 Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
3 Central Vivarium, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic
4 Department of Public Health, Faculty of Military Health Sciences, University of Defence, Hradec Králové, Czech Republic

Guinea pigs were intoxicated intramuscularly with different doses of soman, and cholinesterase activities were determined in the blood, diaphragm and parts of the brain - the pontomedullar area, the frontal cortex and the basal ganglia. The time course of poisoning following low doses (1,3, 5 μg/kg) and a dose equal to 1×LD50 (28.5 μg/kg) were studied. The dose having a negligible effect on cholinesterases in the tissues studied was assessed at 1-3 μg/kg, and, following administration of a dose of 5 μg/kg, statistically significant blood cholinesterase inhibition was demonstrated.

Keywords: blood; brain parts; cholinesterases; guinea pig; soman; inhibition in vivo

Received: April 28, 2010; Revised: May 18, 2010; Published: March 31, 2011  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Bajgar J, Kassa J, Pohanka M, ®ďárová Karasová J, Novotný L, Fusek J, Bláha V. Inhibition of blood and tissue cholinesterases by soman in guinea pigs in vivo. J Appl Biomed. 2011;9(1):35-41. doi: 10.2478/v10136-009-0030-8.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Bajgar J. The influence of inhibitors and other factors on cholinesterases. Sbor Ved Pr LFUK (Hradec Králové). 34: 3-75, 1991.
    2. Bajgar J. Biological monitoring of exposure to nerve agents. Br J Ind Med. 49: 648-653, 1992. Go to original source... Go to PubMed...
    3. Bajgar J. Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis and treatment. Adv Clin Chem. 38: 151-216, 2004. Go to original source... Go to PubMed...
    4. Bajgar J, ©evelová L, Krejčová G, Fusek J, Vachek J, Kassa J, Herink J, de Jong LPA, Benschop HP. Biochemical and behavioral effects of soman vapours in low concentrations. Inhal Toxicol. 16: 497-507, 2004. Go to original source... Go to PubMed...
    5. Bajgar J, Hajek P, Slizova D, Krs O, Fusek J, Kuca K, Jun D, Bartosova L, Blaha V. Changes of acetylcholinesterase activity in different brain areas following intoxication with nerve agents: biochemical and histochemical study. Chem Biol Interact. 165: 14-21, 2007. Go to original source... Go to PubMed...
    6. Bajgar J, Fusek J, Kassa J, Jun D, Kuca K, Hajek P. An attempt to assess functionally minimal acetylcholinesterase activity necessary for survival of rats intoxicated with nerve agents. Chem Biol Interact. 175: 281-285, 2008. Go to original source... Go to PubMed...
    7. Bajgar J, Jun D, Kuča K, Fusek J, ®ďárová Karasová J, Kassa J, Cabal J, Bláha V. Inhibition of blood cholinesterase by nerve agents in vitro. J Appl Biomed. 7: 201-206, 2009. Go to original source...
    8. Clement JG. Survivors of soman poisoning: recovery of the soman LD50 to control value in the presence of extensive acetylcholinesterase inhibition. Arch Toxicol. 63: 150-154, 1989. Go to original source... Go to PubMed...
    9. Clement JG, Hand BT, Shilhoff JD. Differences in the toxicity of soman in various strains of mice. Fundam Appl Toxicol. 1: 419-420, 1981. Go to original source... Go to PubMed...
    10. DeMar JC, Clarkson ED, Ratcliffe RH, Campbell AJ, Thangavelu SG, Herdman CA, Leader H, Schulz SM, Marek E, Medynets MA, Ku TC, Evans SA et al. Pro-2-PAM therapy for central and peripheral cholinesterases. Chem Biol Interact. 187: 191-198, 2010. Go to original source... Go to PubMed...
    11. Ellman GL, Courtney DK, Andres V, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 7: 88-95, 1961. Go to original source... Go to PubMed...
    12. Fawcett WP, Aracava Y, Adler M, Pereira EFR, Albuquerque EX. Acute toxicity of organophosphorus compounds in guinea pigs is sex- and age-dependent and cannot be solely accounted for by acetylcholinesterase inhibition. J Pharmacol Exp Ther. 328: 516-524, 2009. Go to original source... Go to PubMed...
    13. Jokanović M. Liver esterases and soman toxicity in the rat following partial hepatectomy. Biochem Pharmacol. 39: 797-799, 1990. Go to original source... Go to PubMed...
    14. Jokanović M. Current understanding of the mechanisms involved in metabolic detoxification of warfare nerve agents. Toxicol Lett. 188: 1-10, 2009. Go to original source... Go to PubMed...
    15. Kadar T, Raveh L, Cohen G, Oz N, Baraness I, Balan A, Ashani Y, Shapira S. Distribution of 3H-soman in mice. Arch Toxicol. 58: 45-49, 1985. Go to original source... Go to PubMed...
    16. Koplovitz I, Gresham VC, Dochterman LW, Kaminskis A, Stewart JR. Evaluation of the toxicity, pathology, and treatment of cyclohexylmethylphosphonofluoridate (CMPF) poisoning in rhesus monkeys. Arch Toxicol. 66: 622-628, 1992. Go to original source... Go to PubMed...
    17. Kuča K, Pícha J, Cabal J, Liąka F. Synthesis of the three monopyridinium oximes and evaluation of their potency to reactivate acetylcholinesterase inhibited by nerve agents. J Appl Biomed. 2: 51-56, 2004. Go to original source...
    18. Mamczarz J, Pereira EFR, Aracava Y, Adler M, Albuquerque EX. An acute exposure to a sub-lethal dose of soman triggers anxiety-related behavior in guinea pigs: interaction with acute restraint. Neurotoxicology. 31: 77-84, 2010. Go to original source... Go to PubMed...
    19. Morita H, Yanagisava N, Nakajima T, Shimizu M, Hirabayashi H, Okudera H, Nohara M, Midorikawa Y, Mimura S. Sarin poisoning in Matsumoto, Japan. Lancet. 346: 290-293, 1995. Go to original source... Go to PubMed...
    20. Musílek K, Kuča K, Jun D, Doleľal M. In vitro reactivation potency of bispyridinium (E)-but-2-ene linked acetylcholinesterase reactivators against tabun-inhibited acetylcholinesterase. J Appl Biomed. 5: 25-30, 2007. Go to original source...
    21. Novotný L, Misík J, ®ďárová Karasová J, Kuča K, Bajgar J. Influence of different ways of euthanasia on the activity of cholinesterases in the rat. J Appl Biomed. 7: 133-136, 2009. Go to original source...
    22. Nozaki H, Hori S, Shinozawa Y, Fujishima S, Takuma K, Kimura H, Suzuki M, Aikawa N. Relationship between pupil size and acetylcholinesterase activity in patients exposed to sarin vapor. Intensive Care Med. 23: 1005-1007, 1997. Go to original source... Go to PubMed...
    23. Okumura T, Takasu N, Ishimatsu S, Miyanoki S, Mitsuhashi A, Kumada K, Tanaka K, Hinohara S. Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med. 28: 129-135, 1996. Go to original source... Go to PubMed...
    24. Patočka J. Military Toxicology (in Czech). Grada Publishing and Avicenum, Prague, 2004, 178 pp.
    25. Patočka J, Cabal J, Kuča K, Jun D. Oxime reactivation of acetylcholinesterase inhibited by toxic phosphorus esters: in vitro kinetics and thermodynamics. J Appl Biomed. 3: 91-99, 2005. Go to original source...
    26. Shih TM, Penetar DM, McDonough JH, Romano JA, King JM. Age-related differences in soman toxicity and in blood and regional cholinesterase activity. Brain Res Bull. 24: 429-436, 1990. Go to original source... Go to PubMed...
    27. Shih TM, Kan RK, McDonough JH. In vivo cholinesterase inhibitory specificity of organophosphorus nerve agents. Chem Biol Interact. 157-158: 293-303, 2005. Go to original source... Go to PubMed...
    28. Shih TM, Skovira JW, McDonough JH. Effects of 4-pyridine aldoxime on nerve agent inhibited acetylcholinesterase activity in guinea pigs. Arch Toxicol. 83: 1083-1089, 2009a. Go to original source... Go to PubMed...
    29. Shih TM, Skovira JW, O'Donnell JC, McDonough JH. Evaluation of nine oximes on in vivo reactivation of blood, brain, and tissue cholinesterase activity inhibited by organophosphorus nerve agents at lethal dose. Toxicol Mech Methods. 19: 386-400, 2009b. Go to original source... Go to PubMed...
    30. Skopec F, Bajgar J. Anticholinesterase action of organophosphates: importance of the liver. Sbor Ved Pr LFUK (Hradec Králové). 36: 83-92, 1993.
    31. Sterri SH, Fonnum F. Detoxification of organophosphorus compounds. Acta Pharmacol Toxicol (Copenh). 49 (Suppl. 1): 89, 1981.
    32. ®ďárová Karasová J, Bajgar J, Novotný L, Kuča K. Is a high dose of Huperzine A really suitable for pretreatment against high doses of soman? J Appl Biomed. 7: 93-99, 2009a. Go to original source...
    33. Zdarova Karasova J, Bajgar J, Jun D, Pavlikova R, Kuca K. Time-course changes of acetylcholinesterase activity in blood and some tissues in rats after intoxication by Russian VX. Neurotox Res. 16: 356-360, 2009b. Go to original source... Go to PubMed...

    Return to the content