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Altered Metabolomic Profiles May Be Associated with Sevoflurane-Induced Neurotoxicity in Neonatal Rats

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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.

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Acknowledgments

This work was supported by Natural Science Foundation of China (to Jun Zhang, No. 81171020). Thanks for assistance of Biotree Biotechnology Co. Ltd (Shanghai, China) on GC–MS analysis.

Conflict of interest

Bin Liu, Yuechao Gu, Hongyan Xiao, Xi Lei, Weimin Liang and Jun Zhang reported no conflicts of interest.

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    Authors and Affiliations

    1. Department of Anesthesiology, Huashan Hospital, Fudan University, No. 12 Wulumuqi Middle Road, Jin’an District, Shanghai, 200040, People’s Republic of China

      Bin Liu, Hongyan Xiao, Xi Lei, Weimin Liang & Jun Zhang

    2. Department of Anesthesiology, Shanghai Cancer Hospital, Fudan University, Shanghai, 200032, People’s Republic of China

      Yuechao Gu

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    1. Bin Liu
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    Correspondence to Jun Zhang.

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    Bin Liu and Yuechao Gu have contributed equally to this work.

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    Liu, B., Gu, Y., Xiao, H. et al. Altered Metabolomic Profiles May Be Associated with Sevoflurane-Induced Neurotoxicity in Neonatal Rats. Neurochem Res 40, 788–799 (2015). https://doi.org/10.1007/s11064-015-1529-x

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