title: Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation.
abstract: BACKGROUND
  Oxidative stress with dysregulated inflammation are hallmarks of sepsis. Zinc and selenium have important antioxidant functions, such that they could be important in patients with sepsis. We used an in vitro approach to assess the effect of zinc and selenium on oxidative stress, mitochondrial function, and inflammatory responses in conditions mimicking sepsis and related the findings to plasma concentrations and biomarkers in patients with and without sepsis.
  
  
  METHODS
  Human endothelial cells were exposed to a range of zinc and selenium concentrations in conditions mimicking sepsis. Zinc, selenium, and a series of biomarkers of oxidative stress and inflammation were measured in plasma from critically ill patients with and without sepsis.
  
  
  RESULTS
  Culturing cells with different concentrations of zinc caused altered zinc transporter protein expression and cellular zinc content, and selenium affected glutathione peroxidase 3 activity. Although zinc or selenium at physiological concentrations had no effect on interleukin-6 release in vitro, higher concentrations of the trace elements were associated with improved mitochondrial function. Plasma zinc and selenium concentrations were low in patients [zinc: median (range) 4.6 (2.1-6.5) μM in control patients without sepsis and 3.1 (1.5-5.4) μM in patients with sepsis, P=0.002; and selenium: 0.78 (0.19-1.32) μM in control patients and 0.42 (0.22-0.91) μM in sepsis patients, P=0.0009]. Plasma concentrations of interleukin-6, other biomarkers of inflammation, and markers of oxidative damage to proteins and lipids were elevated, particularly in patients with sepsis, and were inversely related to plasma zinc and selenium concentrations.
  
  
  CONCLUSIONS
  Zinc and selenium concentrations were reduced in critically ill patients, with increased oxidative stress and inflammatory biomarkers, particularly in patients with sepsis. Oxidative stress as a result of suboptimal selenium and zinc concentrations might contribute to damage of key proteins.
  
  
  BACKGROUND
  ClinicalTrials.gov: registration number NCT01328509.
authors.affiliation: Academic Unit of Anaesthesia and Intensive Care, School of Medicine & Dentistry and.
authors.forename: K
authors.initials: K
authors.lastname: Mertens
authors.affiliation: Academic Unit of Anaesthesia and Intensive Care, School of Medicine & Dentistry and.
authors.forename: D A
authors.initials: DA
authors.lastname: Lowes
authors.affiliation: Academic Unit of Anaesthesia and Intensive Care, School of Medicine & Dentistry and.
authors.forename: N R
authors.initials: NR
authors.lastname: Webster
authors.affiliation: The Heart Research Institute and Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Talib
authors.affiliation: The Heart Research Institute and Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Hall
authors.affiliation: The Heart Research Institute and Faculty of Medicine, University of Sydney, Sydney, NSW, Australia Present address: Panum Institute, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3, Copenhagen N DK-2200, Denmark.
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Beattie
authors.affiliation: Academic Unit of Anaesthesia and Intensive Care, School of Medicine & Dentistry and h.f.galley@abdn.ac.uk.
authors.forename: H F
authors.initials: HF
authors.lastname: Galley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism*; D002478:Cells, Cultured; D016638:Critical Illness; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress; D012643:Selenium / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult; D015032:Zinc / Q000097:blood / Q000172:deficiency* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015850:Interleukin-6; D005979:Glutathione Peroxidase; D012643:Selenium; D015032:Zinc
keywords: critical illness; mitochondria, oxidative damage; selenium; sepsis; zinc