Reed Beth A, Sabourin Carol L, Lenz David E
Battelle Memorial Institute, Columbus, OH, 43201-2693, USA.
DEL Consulting, Columbus, OH, 43204, USA.
J Biochem Mol Toxicol. 2017 May;31(5). doi: 10.1002/jbt.21886. Epub 2017 Feb 22.
Acetylcholinesterase is vital for normal operation of many processes in the body. Following exposure to organophosphorus (OP) nerve agents, death can ensue without immediate medical intervention. Current therapies mitigate the cholinergic crisis caused by nerve agents but do not fully prevent long-term health concerns, for example, brain damage following seizures. Human butyrylcholinesterase (HuBChE) is a stoichiometric bioscavenger being investigated as an antidote for OP nerve agent poisoning. HuBChE sequesters OP nerve agent in the bloodstream preventing the nerve agent from reaching critical target organ systems. HuBChE was effective when used as both a pre-treatment and as a post-exposure therapy. HuBChE has potential for use in both military settings and to protect civilian first responders in situations where nerve agent usage is suspected. We reviewed various animal models studies evaluating the efficacy of HuBChE against nerve agent exposure, pursuant to its submission for approval under the FDA Animal Rule.
乙酰胆碱酯酶对于身体许多生理过程的正常运作至关重要。接触有机磷（OP）神经毒剂后，若不立即进行医疗干预，可能会导致死亡。目前的治疗方法可缓解由神经毒剂引起的胆碱能危象，但不能完全预防长期健康问题，例如癫痫发作后的脑损伤。人丁酰胆碱酯酶（HuBChE）是一种化学计量生物清除剂，正作为OP神经毒剂中毒的解毒剂进行研究。HuBChE在血液中隔离OP神经毒剂，防止神经毒剂到达关键靶器官系统。HuBChE在用作预处理和暴露后治疗时均有效。HuBChE有潜力用于军事环境以及在怀疑使用神经毒剂的情况下保护平民急救人员。根据其根据美国食品药品监督管理局动物规则提交的批准申请，我们回顾了各种评估HuBChE对抗神经毒剂暴露疗效的动物模型研究。
