{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:51:52Z","timestamp":1787619112637,"version":"build-2736575974"},"reference-count":83,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Systemic molecular responses to pathogen-associated molecular patterns and their modulation by antioxidants are poorly understood in humans. Here, we present a two-stage clinical interventional study in healthy humans challenged with lipopolysaccharide. In the first step, the kinetics of inflammatory modulators within 8 h were investigated by plasma proteomics and lipidomics. In a second step, the effects of a placebo-controlled antioxidant intervention on the individual responses prior to another lipopolysaccharide challenge were determined. Plasma proteomics revealed an early involvement of the endothelium and platelets, followed by the induction of liver-derived acute phase proteins and an innate immune cell response. Untargeted lipidomics revealed an early release of fatty acids and taurocholic acid, followed by complex regulatory events exerted by oxylipins. The consistent lipopolysaccharide-induced downregulation of lysophospholipids suggested the involvement of the Lands cycle, and the downregulation of deoxycholic acid reinforced emerging links between the inflammasome and bile acids. Groups of molecules with similar kinetics to lipopolysaccharide challenge were observed to share precursors, synthesizing enzymes or cellular origin. Dietary antioxidant supplementation prior to lipopolysaccharide challenge had no detectable effect on protein kinetics but significantly downregulated pro-inflammatory sphingosine-1-phosphate and increased levels of oxylipins, 20-HEPE, and 22-HDoHE, which have been described to facilitate the resolution of inflammation. The present study identified a complex network of lipid mediators deregulated in plasma upon lipopolysaccharide challenge and highlighted the role of platelets, endothelial cells, and erythrocytes as potential inflammatory modulators. While dietary antioxidant supplementation hardly affected the initiation of inflammation, it may exert its effects supporting the resolution of inflammation.<\/jats:p>","DOI":"10.3390\/antiox14050536","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T03:50:43Z","timestamp":1746071443000},"page":"536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6782-4117","authenticated-orcid":false,"given":"Gerhard","family":"Hagn","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"},{"name":"Vienna Doctoral School in Chemistry (DoSChem), University of Vienna, Waehringer Stra\u00dfe 42, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7053-8856","authenticated-orcid":false,"given":"Andrea","family":"Bileck","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"},{"name":"Joint Metabolome Facility, University of Vienna and the Medical University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mohr","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-7768","authenticated-orcid":false,"given":"Doreen","family":"Schmidl","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1509-7127","authenticated-orcid":false,"given":"David M.","family":"Baron","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Clinical Division of General Anaesthesia and Intensive Care Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Jilma","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopold","family":"Schmetterer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore"},{"name":"Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore"},{"name":"SERI-NTU Advanced Ocular Engineering (STANCE), Singapore 168751, Singapore"},{"name":"School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore"},{"name":"Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Institute of Molecular and Clinical Ophthalmology, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Garh\u00f6fer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4964-0642","authenticated-orcid":false,"given":"Christopher","family":"Gerner","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"},{"name":"Joint Metabolome Facility, University of Vienna and the Medical University of Vienna, Waehringer Stra\u00dfe 38, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1167\/iovs.13-13784","article-title":"Retinal hemodynamic effects of antioxidant supplementation in an endotoxin-induced model of oxidative stress in humans","volume":"55","author":"Told","year":"2014","journal-title":"Investig. 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