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This study was conducted to investigate the mechanism of potential neurotoxicity on their offspring generation after sevoflurane anesthesia in adult animals during pregnancy based on metabolomics. 16 pregnant rats were equally assigned to sevoflurane group and control group, and serum samples were collected from their 7\u2010day\u2010old offspring for metabolomics analysis using ultra performance liquid chromatography coupled to time\u2010of\u2010flight mass spectrometry. Principal component analysis and partial least squares\u2010discriminate analysis were used for pattern recognition, and pathway analysis was performed by MetaboAnalyst platform. 29 metabolites were discovered as neurotoxicity related\u2010biomarkers, among which S\u2010Adenosylmethioninamine was inhibited dramatically after sevoflurane exposure. Prenatal exposure to sevoflurane led to a significant reduction in S\u2010Adenosylmethionine level, as shown by enzyme\u2010linked immunosorbent assay. Pathway analysis highlighted that prenatal exposure to sevoflurane induced alteration in arginine\/proline metabolism, cysteine\/methionine metabolism, and so on. The most important altered metabolic pathway was arginine\/proline metabolism. This study suggests that abnormal methylation and disturbed arginine\/proline metabolism may crucially contribute to the mechanism with neurotoxicity on offspring generation after sevoflurane anesthesia in adult animals during pregnancy, and dietary supplement of S\u2010Adenosylmethionine and modulating arginine\/proline metabolism may be the potential therapeutic targets for protecting neurodevelopment from detrimental effects of prenatal exposure to inhalational anesthetics.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2017.08.001","type":"journal-article","created":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T07:00:20Z","timestamp":1503558020000},"page":"46-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Potential neurotoxicity of prenatal exposure to sevoflurane on offspring: Metabolomics investigation on neurodevelopment and underlying mechanism"],"prefix":"10.1002","volume":"62","author":[{"given":"Jialong","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Anhui Medical University Hefei 230022 Anhui PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Association of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine No. 111 Dade Road Guangzhou Guangdong 510120 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Anhui Medical University Hefei 230022 Anhui PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Xiao","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University Guangzhou 510006 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200030 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200030 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200030 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikai","family":"Yan","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University Guangzhou 510006 PR China"},{"name":"School of Pharmacy, Shanghai Jiao Tong University Shanghai 200240 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The First Affiliated Hospital of Anhui Medical University Hefei 230022 Anhui PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,24]]},"reference":[{"key":"e_1_2_3_2_1","first-page":"210","article-title":"Effects of allantoin on cognitive function and hippocampal neurogenesis Food and chemical toxicology","volume":"64","author":"Ahn Y.J.","year":"2014","journal-title":"Int. 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