Efficacy and physiological effects of human butyrylcholinesterase as a post-exposure therapy against percutaneous poisoning by VX in the guinea-pig

Chemico-Biological Interactions

Volumn 187, Issue 1-3, 2010, Pages 304-308

  Mumford, Helen ^a   Price, Matthew E ^a   Cerasoli, Douglas M ^b   Teschner, Wolfgang ^c   Ehrlich, Hartmut ^c   Schwarz, Hans Peter ^c   Lenz, David E ^b  

^a DEFENCE SCIENCE AND TECHNOLOGY LABORATORY   (United Kingdom)

^b US ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE   (United States)

^c Baxter Innovations GmbH Industriestr   (Austria)

Author keywords

Bioscavenger; Guinea pig; Nerve agent; Percutaneous

Indexed keywords

CHOLINESTERASE; METHYLPHOSPHONOTHIOIC ACID S (2 DIISOPROPYLAMINOETHYL) O ETHYL ESTER;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BODY TEMPERATURE MONITORING; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; ELECTROENCEPHALOGRAPHY; GUINEA PIG; HEART RATE; INTOXICATION; LD 50; LETHALITY; MALE; NONHUMAN; ONSET AGE; SKIN; SURVIVAL RATE; SURVIVAL TIME; TELEMETRY; THERAPY DELAY; TREATMENT RESPONSE;

ANIMALIA; CAVIA;

EID: 77955516216     PISSN: 00092797     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cbi.2010.02.020     Document Type: Article

References (22)

1. Allon N., Raveh L., Gilat E., Cohen E., Grunwald J., Ashani Y. Prophylaxis against soman inhalation toxicity in guinea pigs by pretreatment alone with human serum butyrylcholinesterase. Toxicol. Sci. 1998, 43:121-128.
2. Armstrong S.J., Graham S.J., Wetherell J.R., Troyer J.K. Recombinant butyrylcholinesterase as a post-poisoning therapy for percutaneous VX poisoning. Proceedings of the 16th Biennial Medical Defense Bioscience Review 2008, 140.
3. Broomfield C.A., Maxwell D.M., Solana R.P., Castro C.A., Finger A.V., Lenz D.E. Protection by butyrylcholinesterase against organophosphorus poisoning in nonhuman-primates. J. Pharmacol. Exp. Ther. 1991, 259:633-638.
4. Castro C.A., Gresham V.C., Finger A.V., Maxwell D.M., Solana R.P., Lenz D.E., Broomfield C.A. Behavioral decrements persist in Rhesus-monkeys trained on a serial probe recognition task despite protection against soman lethality by butyrylcholinesterase. Neurotoxicol. Teratol. 1994, 16:145-148.
5. Cerasoli D.M., Griffiths E.M., Doctor B.P., Saxena A., Fedorko J.M., Greig N.H., Yu Q.S., Huang Y., Wilgus H., Karatzas C.N., Koplovitz I., Lenz D.E. In vitro and in vivo characterization of recombinant human butyrylcholinesterase (Protexia™) as a potential nerve agent bioscavenger. Chem. Biol. Interact. 2005, 157:363-365.
6. Joosen M.J.A., van der Schans M.J., van Helden H.P.M. Percutaneous exposure to VX: clinical signs, effects on brain acetylcholine levels and EEG. Neurochem. Res. 2008, 33:308-317.
7. Katos A.M., Conti M.L., Moran T.S., Gordon R.K., Doctor B.P., Sciuto A.M., Nambiar M.P. Abdominal bloating and irritable bowel syndrome like symptoms following microinstillation inhalation exposure to chemical warfare nerve agent VX in guinea pigs. Toxicol. Ind. Health 2007, 23:231-240.
8. Kolarich D., Weber A., Pabst M., Stadlmann J., Teschner W., Ehrlich H., Schwarz H.P., Altmann F. Glycoproteomic characterization of butyrylcholinesterase from human plasma. Proteomics 2008, 8:254-263.
9. J.P. Langenberg, H.P. Benschop, M.J. van der Schans, L.P.A. De Jong, Effect of pretreatment with human butyrylcholinesterase scavengers on the toxicokinetics and binding of nerve agents in guinea pigs and marmosets. Award no. DAMD17-00-2-0032, Prepared for: U.S. Army Medical Research and Materiel Command, Fort Detrick, Maryland 217-5012, Accessed via Public Technical Reports at DTIC Online (), 1-50, 2002. http://www.dtic.mil/dtic/index.html.
10. Lenz D.E., Broomfield C.A., Maxwell D.M., Cerasoli D.M. Nerve agent bioscavengers: protection against high- and low-dose organophosphorus exposure. Chemical Warfare Agents: Toxicity at Low Levels 2001, 245-260. CRC Press, Boca Raton. S. Somani, J.A. Romano (Eds.).
11. Lenz D.E., Maxwell D.M., Koplovitz I., Clark C.R., Capacio B.R., Cerasoli D.M., Federko J.M., Luo C.Y., Saxena A., Doctor B.P., Olson C. Protection against soman or VX poisoning by human butyrylcholinesterase in guinea pigs and cynomolgus monkeys. Chem. Biol. Interact. 2005, 157:205-210.
12. Mumford H., Lenz D.E., Cerasoli D.M., Price M.E., Graham S.J., Wetherell J.R. A preliminary assessment of pretreatment with human butyrylcholinesterase on the physiological effects of percutaneous VX challenge in the guinea-pig. Proceedings of the 16th Biennial Medical Defense Bioscience Review 2008, 43.
13. Mumford H., Price M.E., Wetherell J.R. A novel approach to assessing percutaneous VX poisoning in the conscious guinea-pig. J. Appl. Toxicol. 2008, 28:694-702.
14. Saxena A., Sun W., Dabisch P.A., Hulet S.W., Hastings N.B., Jakubowski E.M., Mioduszewski R.J., Doctor B.P. Efficacy of human serum butyrylcholinesterase against sarin vapor. Chem. Biol. Interact. 2008, 175:267-272.
15. Sidell F.R. Nerve agents. Medical Aspects of Chemical and Biological Warfare 1997, 138. Borden Institute, Washington, DC. F.R. Sidell, E.T. Takafuji, D.R. Franz (Eds.).
16. Sun W., Doctor B.P., Lenz D.E., Saxena A. Long-term effects of human butyrylcholinesterase pretreatment followed by acute soman challenge in cynomolgus monkeys. Chem. Biol. Interact. 2008, 175:428-430.
17. Sun W., Doctor B.P., Saxena A. Safety and pharmacokinetics of human serum butyrylcholinesterase in guinea pigs. Chem. Biol. Interact. 2005, 157:428-429.
18. Tenn C.C., Mikler J.R., Hill I., Weatherby K., Garrett M., Caddy N., Stewart C., Karatzas C.N., Huang Y., Troyer J.K., Lundy P.M., Sawyer T.W. Recombinant human butyrylcholinesterase as a therapeutic agent to counteract the effects of VX toxicity in domestic swine. J. Med. Chem. Def. 2008, 6.
19. van der Schans M.J., Lander B.J., van der Wiel H., Langenberg J.P., Benschop H.P. Toxicokinetics of the nerve agent (+/-)-VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration. Toxicol. Appl. Pharmacol. 2003, 191:48-62.
20. Wetherell J., Hall T., Passingham S. Physostigmine and hyoscine improves protection against the lethal and incapacitating effects of nerve agent poisoning in the guinea-pig. Neurotoxicology 2002, 23:341-349.
21. Wetherell J., Price M., Mumford H., Armstrong S., Scott L. Development of next generation medical countermeasures to nerve agent poisoning. Toxicology 2007, 233:120-127.
22. Huang Y.-J., Lundy P.M., Lazaris A., Huang Y., Baldassarre H., Wang B., Turcotte C., Cote M., Bellemare A., Bilodeau A.S., Brouillard S., Touati M., Herskovits P., Begin I., Neveu N., Brochu E., Pierson J., Hockley D.K., Cerasoli D.M., Lenz D.E., Wilgus H., Karatzas C.N., Langermann S. Substantially improved pharmacokinetics of recombinant human butyrylcholinesterase by fusion to human serum albumin. BMC Biotechnol. 2008, 8:50.