ArticleAntioxidants (Basel, Switzerland)2025
Time Course of Plasma Proteomic and Oxylipin Changes Induced by LPS Challenge and Modulated by Antioxidant Supplementation in a Randomized Controlled Trial.
Article in Antioxidants (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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1 citing paper in PubMed.
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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