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Euxanthone Ameliorates Sevoflurane-Induced Neurotoxicity in Neonatal Mice.
J Mol Neurosci. 2019 Jun; 68(2):275-286.JM

Abstract

Sevoflurane is a widely used anesthetic. A series of recent studies have shown that exposure to sevoflurane at an early stage is a risk factor for the development of learning and memory dysfunction. Euxanthone is a xanthone derivative obtained from Polygala caudata. This study was designed to investigate whether euxanthone can confer neuroprotective activities against sevoflurane-induced neurotoxicity and to determine the associated molecular mechanisms. Neonatal Sprague-Dawley (male) rats were exposed to sevoflurane with or without euxanthone treatment. The behavioral data of rats were collected at P41 (the beginning of the adult stage). The hippocampal tissue was obtained following exposure to sevoflurane. The reactive oxygen species (ROS) level in the hippocampal tissue was determined by a commercial kit. The expression of apoptotic markers and inflammatory cytokines was determined by western blot. The mRNA and protein expression of Nrf2 were determined by qRT-PCR and western blot, respectively. The rat in vitro model of neurotoxicity was established using isolated hippocampal neurons. Nrf2 expression was repressed by transfection of siRNA. The cell viability was assessed by the CCK-8 assay. The flow cytometry was performed to measure apoptotic cell death. Our data showed that euxanthone treatment at the neonatal stage protected against sevoflurane-induced neurotoxicity in adult rats. At the molecular level, our findings revealed that the neuroprotective activities of euxanthone were associated with decreased sevoflurane-induced apoptosis cell death and neuroinflammation. More importantly, our results provide the experimental evidence that euxanthone confers neuroprotection by upregulating Nrf2 expression. Euxanthone has a therapeutic potential for clinical prevention of sevoflurane-induced neurotoxicity.

Authors+Show Affiliations

Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 JingWu Road, Jinan, 250021, China.Department of Dermatology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 JingWu Road, Jinan, 250021, China. gongmingwangjnsd@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30927203

Citation

Zhou, Hui, et al. "Euxanthone Ameliorates Sevoflurane-Induced Neurotoxicity in Neonatal Mice." Journal of Molecular Neuroscience : MN, vol. 68, no. 2, 2019, pp. 275-286.
Zhou H, Li S, Wang G. Euxanthone Ameliorates Sevoflurane-Induced Neurotoxicity in Neonatal Mice. J Mol Neurosci. 2019;68(2):275-286.
Zhou, H., Li, S., & Wang, G. (2019). Euxanthone Ameliorates Sevoflurane-Induced Neurotoxicity in Neonatal Mice. Journal of Molecular Neuroscience : MN, 68(2), 275-286. https://doi.org/10.1007/s12031-019-01303-1
Zhou H, Li S, Wang G. Euxanthone Ameliorates Sevoflurane-Induced Neurotoxicity in Neonatal Mice. J Mol Neurosci. 2019;68(2):275-286. PubMed PMID: 30927203.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Euxanthone Ameliorates Sevoflurane-Induced Neurotoxicity in Neonatal Mice. AU - Zhou,Hui, AU - Li,Song, AU - Wang,Gongming, Y1 - 2019/03/30/ PY - 2019/01/24/received PY - 2019/03/15/accepted PY - 2019/3/31/pubmed PY - 2019/6/5/medline PY - 2019/3/31/entrez KW - Apoptosis KW - Euxanthone KW - Neuroinflammation KW - Neurotoxicity KW - Nrf2 KW - Sevoflurane SP - 275 EP - 286 JF - Journal of molecular neuroscience : MN JO - J. Mol. Neurosci. VL - 68 IS - 2 N2 - Sevoflurane is a widely used anesthetic. A series of recent studies have shown that exposure to sevoflurane at an early stage is a risk factor for the development of learning and memory dysfunction. Euxanthone is a xanthone derivative obtained from Polygala caudata. This study was designed to investigate whether euxanthone can confer neuroprotective activities against sevoflurane-induced neurotoxicity and to determine the associated molecular mechanisms. Neonatal Sprague-Dawley (male) rats were exposed to sevoflurane with or without euxanthone treatment. The behavioral data of rats were collected at P41 (the beginning of the adult stage). The hippocampal tissue was obtained following exposure to sevoflurane. The reactive oxygen species (ROS) level in the hippocampal tissue was determined by a commercial kit. The expression of apoptotic markers and inflammatory cytokines was determined by western blot. The mRNA and protein expression of Nrf2 were determined by qRT-PCR and western blot, respectively. The rat in vitro model of neurotoxicity was established using isolated hippocampal neurons. Nrf2 expression was repressed by transfection of siRNA. The cell viability was assessed by the CCK-8 assay. The flow cytometry was performed to measure apoptotic cell death. Our data showed that euxanthone treatment at the neonatal stage protected against sevoflurane-induced neurotoxicity in adult rats. At the molecular level, our findings revealed that the neuroprotective activities of euxanthone were associated with decreased sevoflurane-induced apoptosis cell death and neuroinflammation. More importantly, our results provide the experimental evidence that euxanthone confers neuroprotection by upregulating Nrf2 expression. Euxanthone has a therapeutic potential for clinical prevention of sevoflurane-induced neurotoxicity. SN - 1559-1166 UR - https://www.unboundmedicine.com/medline/citation/30927203/Euxanthone_Ameliorates_Sevoflurane_Induced_Neurotoxicity_in_Neonatal_Mice_ L2 - https://dx.doi.org/10.1007/s12031-019-01303-1 DB - PRIME DP - Unbound Medicine ER -