The Effect of N-Acetylcysteine on The Neurotoxicity of Sevoflurane in Developing Hippocampus Cells
Esra Adiyeke, Nurten Bakan, Ayca Uvez, Devrim Oz Arslan, Sima Kiliç, Berkcan Koc, Samed Ozer, Ozlem Saatci, Elif Ilkay Armutak, Tugce Turkan Alasirt
Sancaktepe Martyr Prof.Dr. İlhan Varank Training and Research Hospital
Giriş: Sevoflurane is a commonly used inhalational anesthetic for inducing and maintaining general anesthesia in pediatric surgery. However, its administration has been associated with neurodegeneration, raising concerns regarding safety(1,2).This study aimed to investigate the potential protective effects of N-acetylcysteine against sevoflurane-induced neurotoxicity in the developing rat hippocampus.
Gereç ve Yöntem: DESIGN: An experimental randomised animal study.SETTING: Experimental Unit, Acıbadem Mehmet Ali Aydınlar University of Istanbul, Istanbul, Turkiye.ANIMALS: Thirty-two 14-day-old male Wistar rats were used for the experiment.INTERVENTIONS: Rats were randomly received 3 l/min gas (air and 30% oxygen (O2)) for 6 h. 1) Intraperitoneal saline 2) Intraperitoneal administration of 150mg/kg NAC 3) 3% sevoflurane 4) 3% sevoflurane and Intraperitoneal administration of 150mg/kg NAC.MAIN OUTCOME MEASURES:The primary outcome of the study revealed that the administration of N-acetylcysteine alongside sevoflurane contributed to the suppression of neurotoxicity.
Bulgular: In developing hippocampal neuronal cells, sevoflurane (Sev group) and N-acetylcysteine (NAC group) administration alone suppressed autophagy, as evidenced by the reduced protein levels of Beclin-1, p62, and LC3A in hippocampal tissues. However, in the Sev+NAC group, the levels of Beclin-1 and p62 approached those in the control group, indicating continued autophagy. The sev group showed significantly increased protein levels of NLRP3, NRF-2, pNRF2, Caspase-1, and IL-1β compared to the control group. In contrast, these proteins were significantly decreased in the sev+NAC group compared to the control group. Analysis of hippocampal apoptosis revealed that the apoptotic index values of the Sev group were significantly higher than those of the control group, whereas the Sev+NAC group exhibited significantly decreased apoptotic index values compared to the control group.
Tartışma ve Sonuç: This study demonstrated that sevoflurane induced neurotoxicity in developing hippocampus tissue. However, the neurotoxicity was suppressed when N-acetylcysteine was administered in combination with sevoflurane.
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