Overexpression of Nfs1 Cysteine Desulphurase Relieves Sevoflurane‐Induced Neurotoxicity and Cognitive Dysfunction in Neonatal Mice Via Suppressing Oxidative Stress and Ferroptosis

作者：Yang Zhang, Xinru Liu, Lijuan Xie, Jin Young Hong, Zhuang Qin, Li Ren, Xiaohong Li, Congli Zhang · 发表于：Journal of Biochemical and Molecular Toxicology · 年份：2024 · DOI：10.1002/jbt.70051 · 被引用次数：12 · 研究领域：Anesthesia and Neurotoxicity Research、Intensive Care Unit Cognitive Disorders、Electrolyte and hormonal disorders

ABSTRACT Clinical evidence suggests that multiple exposures to sevoflurane in young people may be detrimental to cognitive development. Iron accumulation in the hippocampus is associated with sevoflurane‐induced neurotoxicity and cognitive deficits. The cysteine desulphurase, Nfs1, the rate‐limiting enzyme for the biosynthesis of iron–sulphur clusters, plays a role in cellular iron homeostasis. However, the impact of Nfs1‐mediated ferroptosis on sevoflurane‐induced neurotoxicity and cognitive impairments in neonatal mice remains undetermined. Neonatal mice at postnatal Day 6 received 3% sevoflurane daily for 3 consecutive days. Cognitive function was assessed using the Morris water maze test, and neurotoxicity was evaluated through terminal deoxynucleotidyl transferase dUTP nick end labeling and immunofluorescence staining. Here, HT22 hippocampal neurons were employed for in‐vitro experiments, and Fe 2+ accumulation was measured. Ferroptosis‐related genes, including glutathione peroxidase 4 (GPX4), transferrin receptor 1 (TFR1) and ferritin, in the hippocampus and HT22 cells were observed, along with oxidative stress‐related indicators such as reactive oxygen species (ROS), methionine adenosyltransferase (MAT), glutathione (GSH) and lipid peroxidation (LPO). Transmission electron microscopy was utilized to examine the mitochondrial microstructure. Sevoflurane exposure significantly decreased Nfs1 expression in the hippocampus of mice and HT22 cells. This exposure resulted in ...