Document Detail


Efficacy of human serum butyrylcholinesterase against sarin vapor.
MedLine Citation:
PMID:  18597747     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a pretreatment drug for organophosphate (OP) poisoning in humans. It was shown to protect mice, rats, guinea pigs, and monkeys against multiple LD(50) challenges of OP nerve agents by i.v. or s.c. bolus injections. Since inhalation is the most likely route of exposure to OP nerve agents on the battlefield or in public places, the aim of this study was to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to sarin (GB) vapor. Male Göttingen minipigs were subjected to one of the following treatments: (1) air exposure; (2) GB vapor exposure; (3) pretreatment with 3 mg/kg of Hu BChE followed by GB vapor exposure; (4) pretreatment with 6.5 mg/kg of Hu BChE followed by GB vapor exposure; (5) pretreatment with 7.5 mg/kg of Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection, 24h prior to whole-body exposure to GB vapor at a concentration of 4.1 mg/m(3) for 60 min, a dose lethal to 99% of untreated exposed pigs (LCt99). EEG, ECG, and pupil size were monitored throughout exposure, and blood drawn from a surgically implanted jugular catheter before and throughout the exposure period, was analyzed for acetylcholinesterase (AChE) and BChE activities, and the amount of GB present in plasma. All animals exposed to GB vapor alone or pretreated with 3 or 6.5 mg/kg of Hu BChE, died following exposure to GB vapor. All five animals pretreated with 7.5 mg/kg of Hu BChE survived the GB exposure. The amount of GB bound in plasma was 200-fold higher compared to that from plasma of pigs that did not receive Hu BChE, suggesting that Hu BChE was effective in scavenging GB in blood. Additionally, pretreatment with 7.5 mg/kg of Hu BChE prevented cardiac abnormalities and seizure activity observed in untreated animals and those treated with lower doses of Hu BChE.
Authors:
Ashima Saxena; Wei Sun; Paul A Dabisch; Stanley W Hulet; Nicholas B Hastings; Edward M Jakubowski; Robert J Mioduszewski; Bhupendra P Doctor
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Publication Detail:
Type:  Journal Article     Date:  2008-05-23
Journal Detail:
Title:  Chemico-biological interactions     Volume:  175     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-08     Completed Date:  2008-12-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  267-72     Citation Subset:  IM    
Affiliation:
Division of Biochemistry, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. ashima.saxena@us.army.mil
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MeSH Terms
Descriptor/Qualifier:
Animals
Antidotes / therapeutic use*
Biological Availability
Butyrylcholinesterase / blood*,  pharmacokinetics,  therapeutic use*
Chemical Warfare Agents / toxicity*
Humans
Male
Sarin / toxicity*
Swine
Swine, Miniature
Chemical
Reg. No./Substance:
0/Antidotes; 0/Chemical Warfare Agents; 107-44-8/Sarin; EC 3.1.1.-/Butyrylcholinesterase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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