title: Altered metabolomic profiles may be associated with sevoflurane-induced neurotoxicity in neonatal rats.
abstract: Experimental studies demonstrate that inhaled anesthetics can cause neurodegeneration and neurobehavioral dysfunctions. Evidence suggests changes in cerebral metabolism following inhaled anesthetics treatment can perturb cerebral homeostasis, which may be associated with their induced neurotoxicity. Seven-day-old rat pups were divided into two groups: control group (Group C) and sevoflurane group (Group S, 3 % sevoflurane exposure for 6 h). Gas chromatography-mass spectrometry (GC-MS) was used for analyzed differential metabolites of cerebral cortex in both groups, Also western blot, flow cytometry, enzymatic methods and electron microscopy were performed in various biochemical and anatomical assays. Sevoflurane exposure significantly elevated caspase-3 activation and ROS levels, decreased mitochondrial cardiolipin contents, and changed cellular ultrastructure in the cerebral cortex. Correspondingly, these results corroborated the GC-MS findings which showed altered metabolic pathways of glucose, amino acids, and lipids, as well as intracellular antioxidants and osmolyte systems in neonatal brain following prolonged exposure to high sevoflurane concentration. Our data indicate that sevoflurane anesthesia causes significant oxidative stress, neuroapoptosis, and cellular ultrastructure damage which is associated with altered brain metabotype in the neonatal rat. Our study also confirmed that GC-MS is a strategic and complementary platform for the metabolomic characterization of sevoflurane-induced neurotoxicity in the developing brain.
authors: Department of Anesthesiology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Middle Road, Jin'an District, Shanghai, 200040, People's Republic of China, lbzaixuzhou@126.com.
authors: Bin
authors: B
authors: Liu
authors: Yuechao
authors: Y
authors: Gu
authors: Hongyan
authors: H
authors: Xiao
authors: Xi
authors: X
authors: Lei
authors: Weimin
authors: W
authors: Liang
authors: Jun
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001784:Blood Gas Analysis; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D055432:Metabolomics; D008738:Methyl Ethers / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D008738:Methyl Ethers; D000077149:Sevoflurane