Mumford_2013_Chem.Biol.Interact_203_160

Reference

Title : Human plasma-derived BCHE as a stoichiometric bioscavenger for treatment of nerve agent poisoning - Mumford_2013_Chem.Biol.Interact_203_160
Author(s) : Rice H , Docx CJ , Price ME , Green AC , Tattersall JE , Armstrong SJ
Ref : Chemico-Biological Interactions , 203 :160 , 2013
Abstract :

Potent organophosphorous (OP) agents, such as VX, are hazardous by absorption through the skin and are resistant to conventional pharmacological antidotal treatments. The residence time of a stoichiometric bioscavenger, human butyrylcholinesterase (huBCHE), in the plasma more closely matches that of VX than do the residence times of conventional therapy drugs (oxime, anti-muscarinic, anticonvulsant). Intramuscular (i.m.) huBCHE afforded almost complete protection when administered prior to the onset of observable cholinergic signs of VX poisoning, but once signs of poisoning became evident the efficacy of i.m. huBCHE decreased. A combination of nerve agent therapy drugs (oxime, anti-muscarinic, anticonvulsant) with huBCHE (i.m.) protected 100% (8/8) of guinea-pigs from a lethal dose of VX (0.74mg/kg) to 48h, even when administered on signs of poisoning. Survival was presumed to be due to immediate alleviation of the cholinergic crisis by the conventional pharmacological treatment drugs, in conjunction with bioscavenger that prevented further absorbed agent reaching the AChE targets. Evidence to support this proposed mechanism of action was obtained from PKPD experiments in which multiple blood samples and microdialysate samples were collected from individual conscious ambulatory animals. Plasma concentrations of intramuscularly-administered atropine, diazepam and HI-6 reached a peak within 15min and were eliminated rapidly within 4h. Plasma concentrations of huBCHE administered by the i.m. route took approximately 24h to reach a peak, but were well-maintained over the subsequent 7days. Thus, the pharmacological therapy rapidly treated the initial signs of poisoning, whilst the bioscavenger provided prolonged protection by neutralising further nerve agent entering the bloodstream and preventing it from reaching the target organs.

PubMedSearch : Mumford_2013_Chem.Biol.Interact_203_160
PubMedID: 22981459

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Citations formats

Rice H, Docx CJ, Price ME, Green AC, Tattersall JE, Armstrong SJ (2013)
Human plasma-derived BCHE as a stoichiometric bioscavenger for treatment of nerve agent poisoning
Chemico-Biological Interactions 203 :160

Rice H, Docx CJ, Price ME, Green AC, Tattersall JE, Armstrong SJ (2013)
Chemico-Biological Interactions 203 :160