O-GlcNAcylation levels remain stable regardless of the anesthesia procedure in healthy rats - 25/06/24
, Amandine Vergnaud a, Thomas Pele a, Angélique Blangy-Letheule a, Virginie Aillerie a, Thomas Dupas a, Angelique Erraud b, Persello Antoine a, Jules Lecomte c, Matthieu Rivière d, Arnaud Tessier e, Aurélia Leroux a, Bertrand Rozec f, Manon Denis b, Benjamin Lauzier a, Dorian Hassoun g, Anaïs Maillard a
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Resumen |
Introduction |
Anesthesia is used on a daily basis in Human medicine and for scientific research. Among anesthetic agents, ketamine and isoflurane are the most commonly used for intravenous and inhalation-induced anesthesia, respectively. Still, such anesthetics does affect cell homeostasis through cell signaling pathways with modulations of protein post-translational modifications (PTMs). O-GlcNAcylation (O-GlcNAc) is a ubiquitous PTM involved in many biological processes. Hirose et al. reported that isoflurane could induce an increase in O-GlcNAc levels. However, this study was not designed to specifically evaluate this aspect. Considering that O-GlcNAc stimulation is cardioprotective in acute pathologies, the increase in O-GlcNAc levels induced by anesthesia could potentially have unexpected impact on research projects.
Objective |
Our study aimed to evaluate whether (1) anesthesia influences O-GlcNAc and (2) O-GlcNAc stimulation affects physiological parameters in healthy rats.
Method |
General anesthesia was performed on adult healthy males Wistar rats with either ketamine-xylazine (KX) or isoflurane (ISO) for one hour. Rats were injected either with Ringer Lactate or NButGT (KX+N, ISO+N) treatment (10mg/kg) to increase O-GlcNAc levels. Upon sacrifice, hemodynamics parameters and plasmatic markers were evaluated, and heart was harvested. O-GlcNAc and O-GlcNAc-related enzymes levels were evaluated by western blot.
Results |
As expected, isoflurane had lower impact on hemodynamics parameters. Surprisingly, anesthesia (neither ISO nor KX) had no impact on O-GlcNAc levels in the heart (KX: 0.90±0.18; ISO: 0.87±0.04; P<0.05). Pharmacological stimulation of O-GlcNAc by NButGT efficiently increased O-GlcNAc levels in the heart (KX: 0.90±0.18; KX+N: 1.22±0.16; ISO: 0.87±0.04; ISO+N: 1.32±0.08; P<0.05) and had no impact on physiological parameters such as heart rate, mean blood pressure, blood gazes, electrolytes or pH.
Conclusion |
These results prove that neither ketamine-xylazine nor isoflurane-induced anesthesia increase O-GlcNAc levels under standardized anesthetics conditions. Pharmacological stimulation of O-GlcNAc over a 1-hour period did not disrupt the physiological balance. We also confirm that on healthy rat, acute increase in O-GlcNAc levels does not impact cardiovascular parameters.
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Vol 117 - N° 6-7S
P. S215 - juin 2024 Regresar al número
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- Index
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