{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:18:53Z","timestamp":1778681933360,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004480","name":"Natural Science Foundation of Shanxi Province","doi-asserted-by":"publisher","award":["202403021211125"],"award-info":[{"award-number":["202403021211125"]}],"id":[{"id":"10.13039\/501100004480","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Nitrous oxide (N2O) is increasingly used as a recreational drug, leading to neurological and systemic toxicities. However, due to the rapid elimination and minimal alteration of nitrogen oxides, the short direct detection window complicates the assessment of N2O exposure. Method: In this study, we investigated the effects of chronic N2O exposure on plasma metabolites using an untargeted metabolomics approach in a mouse model. C57BL\/6 mice were exposed to 90,000 ppm N2O (1 h, twice daily for 28 days) or room air. Plasma samples were analyzed via UHPLC -Triple TOF -MS. Orthogonal partial least squares discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) curves were used to identify differential metabolites. Result: A total of 35 differential metabolites were identified. Eight metabolites with an area under the curve (AUC) &gt; 0.90 were selected as candidate biomarkers, including up-regulated SOPC and PC(16:0\/16:0) (suggesting disrupted phospholipid remodeling and membrane integrity), and down-regulated DL-tryptophan, creatine, ectoine, indole, His-Ser, and Ile-Pro. Pathway enrichment analysis revealed significant alterations in glycine, serine and threonine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; protein digestion and absorption; and tryptophan metabolism. Conclusions: Our data indicate that chronic N2O exposure disrupts multiple amino acid-related metabolic pathways (e.g., tryptophan-kynurenine pathway) and phospholipid homeostasis. The identified metabolite changes, along with vitamin B12, homocysteine, and methylmalonic acid, may constitute a specific metabolic fingerprint for N2O exposure. These findings help reveal the intrinsic mechanistic links underlying metabolic disorders induced by N2O exposure.<\/jats:p>","DOI":"10.3390\/metabo16050324","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:46:55Z","timestamp":1778676415000},"page":"324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Nitrous Oxide Exposure Disrupts Metabolism in Mice: A Plasma Untargeted Metabolomics Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Juan","family":"Jia","sequence":"first","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, China"},{"name":"Shanxi Key Laboratory of Forensic Medicine, Jinzhong 030600, China"},{"name":"Shanxi Province Engineering Research Center of Forensic Identification, Jinzhong 030600, China"},{"name":"Key Laboratory of Forensic Toxicology of Ministry of Public Security, Jinzhong 030600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jinan Public Security Bureau Zhangqiu Branch, Jinan 250200, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, China"},{"name":"Shanxi Key Laboratory of Forensic Medicine, Jinzhong 030600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Congying","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keming","family":"Yun","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, China"},{"name":"Shanxi Key Laboratory of Forensic Medicine, Jinzhong 030600, China"},{"name":"Key Laboratory of Forensic Toxicology of Ministry of Public Security, Jinzhong 030600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangwei","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Forensic Medicine, Shanxi Medical University, Jinzhong 030600, China"},{"name":"Shanxi Key Laboratory of Forensic Medicine, Jinzhong 030600, China"},{"name":"Shanxi Province Engineering Research Center of Forensic Identification, Jinzhong 030600, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"k4579","DOI":"10.1136\/bmj.k4579","article-title":"Laughter isn\u2019t always the best medicine","volume":"363","author":"Acharya","year":"2018","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s12640-021-00352-y","article-title":"Recreational Nitrous Oxide Abuse: Prevalence, Neurotoxicity, and Treatment","volume":"39","author":"Xiang","year":"2021","journal-title":"Neurotox. 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