A anestesia com ketamina/xilazina altera a atividade colinesterásica em ratos: uma abordagem in vivo, in vitro e in silico

• Ano de defesa: 2025
• Autor(a) principal: Corrêa, Larissa de Jesus
• Orientador(a): Sampaio, Karla Nívea
• Banca de defesa: Dias Júnior, Carlos Alan Candido , Gonçalves, Rita de Cássia Ribeiro
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso embargado
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; Mestrado em Ciências Farmacêuticas
• Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Farmacêuticas
• Departamento: Centro de Ciências da Saúde
• País: BR
• Palavras-chave em Português: Ketamina; Xilazina; Anestésicos; Acetilcolina; Acetilcolinesterase; Butirilcolinesterase; Ketamine; Xylazine; Anesthetics; Acetylcholine; Acetylcholinesterase; Butyrylcholinesterase
• Área do conhecimento CNPq: Farmácia
• Link de acesso: http://repositorio.ufes.br/handle/10/20742

Introduction: Ketamine and Xylazine (K/X) are veterinary anesthetics commonly used in various procedures, but they can interfere with the body's homeostasis and autonomic balance. Previous studies have observed a reduction in plasma butyrylcholinesterase (BChE) activity with K/X, suggesting possible systemic cholinergic modulation. However, it remains unknown whether this effect extends to other cholinesterases or to different tissues, as well as the possible mechanisms involved in these effects. To elucidate these questions, we integrated in silico, in vitro, and in vivo approaches to investigate the interaction of K/X with cholinesterases and evaluate its effects on enzyme activity and the expression of inflammatory markers. Methods: The in silico study investigated the binding potential of K/X to cholinesterases and predicted interactions with catalytic, anionic, and peripheral residues. In vitro assays evaluated the dose-dependent effect of each drug on erythrocyte acetylcholinesterase (AChE) activity and plasma BChE in control rats. In the in vivo study, Wistar rats (10–12 weeks) were assigned to four protocols: (1) serial blood collection before, during, and after K/X anesthesia and surgery; (2) isolated anesthesia followed by euthanasia 48 h later; (3) control group without prior exposure to anesthesia/surgery; and (4) caudal puncture without anesthesia and euthanasia three days later. Finally, blood, cortex, hippocampus, brainstem, and heart samples were collected for analysis of AChE and BChE, as well as Western blot analysis of TNF-α and NF-κB expression in the left ventricle (LV). Results: Docking indicated weak interactions between cholinesterase residues and ligands. In vitro testing showed dose-dependent inhibition of AChE and BChE in control rats by both anesthetics. Surgery and anesthesia combined reduced plasma BChE activity 24 and 48 hours after anesthesia, and erythrocyte AChE activity 48 hours after anesthesia. Anesthesia alone decreased BChE activity but increased AChE activity. The caudal puncture did not change enzyme activity. Anesthesia with or without surgery increased atrial cholinesterase activity and decreased ChE activity in the left ventricle, brainstem, and prefrontal cortex. TNF-α expression in the LV was decreased by K/X. Conclusions: Anesthetic induction with K/X changes cholinesterase activity in a tissue- and time dependent manner, suggesting a systemic effect on cholinergic tone. The concomitant reduction of TNF-α in the LV indicates a possible link between cholinergic modulation and the inflammatory response.