Butyrylcholinesterase, a stereospecific in vivo bioscavenger against nerve agent intoxication.
Biochem Pharmacol
; 171: 113670, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31628910
ABSTRACT
Human butyrylcholinesterase (E.C. 3.1.1.8) purified from blood plasma has previously been shown to provide protection against up to five and a half times the median lethal dose of an organophosphorus nerve agent in several animal models. In this study the stoichiometric nature of the protection afforded by human butyrylcholinesterase against organophosphorus nerve agents was investigated in guinea pigs. Animals were administered human butyrylcholinesterase (26.15â¯mg/kgâ¯≡â¯308â¯nmol/kg) by the intravascular or intramuscular route. Animals were subsequently dosed with either soman or VX in accordance with a stage-wise adaptive dose design to estimate the modified median lethal dose in treated animals. Human butyrylcholinesterase (308â¯nmol/kg) increased the median lethal dose of soman from 154â¯nmol/kg to 770â¯nmol/kg. Comparing the molar ratio of agent molecules to enzyme active sites yielded a stoichiometric protective ratio of 21 for soman, likely related to the similar stereoselectivity the enzyme has compared to the toxic target, acetylcholinesterase. In contrast, human butyrylcholinesterase (308â¯nmol/kg) increased the median lethal dose of VX from 30â¯nmol/kg to 312â¯nmol/kg, resulting in a stoichiometric protective ratio of only 11, suggesting a lack of stereoselectivity for this agent.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Intoxicação
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Butirilcolinesterase
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Substâncias para a Guerra Química
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Agentes Neurotóxicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos