Study of protective properties of butyrylcholinesterase in acute anticholinesterase poisoning on BChE-KO and BALB/c mice

Abstract

Introduction: The article presents the results of studying the protective properties of recombinant human butyrylcho­linesterase (rhBChE) in a model of acute anticholinesterase poisoning in mice knocked out for the BChE gene. Balb/c inbred mice were also used to demonstrate the important role of BChE.

Materials and methods: In the study, BChE-ko and Balb/c mice were used. An organophosphorus compound (OPC) paraoxon was used as a toxic agent causing acute anticholinesterase poisoning. rhBChE was used as an antidote for OPC poisoning. To obtain rhBChE, an expression system based on CHO cell lines was chosen. In order to suppress BChE in Balb/c mice, a carboxyl esterase blocker cresylbenzodioxaphosphorin oxide (CBDP) was used. Two parame­ters were used to study the recovery after toxicity modeling: the end time of the animal tremor and the distance covered in open-field for 3 minutes.

Results and discussion: The acute poisoning model using the CBDP blocker showed that the sensitivity of Balb/c mice increased significantly. The use of rhBChE against the background of CBDP allowed achieving 100% survival of animals with the minimum lethal dose of paraoxon. Knockout mice are expected to be more sensitive to the toxin, and the use of a biological trap in the form of rhBChE made it possible for 70% of the animals to survive with the minimum lethal dose of paraoxon. Besides, the use of rhBChE facilitated reducing the recovery time after OPC poisoning.

Conclusion: The results of the study showed that the use of rhBChE as a protective agent in acute OPC poisoning significantly increased the survival of the animals and reduced the clinical manifestations of poisoning.