Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation

K Mertens, D A Lowes, N R Webster, J Talib, L Hall, M J Davies, J H Beattie, H F Galley

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: registration number NCT01328509.

Original languageEnglish
Pages (from-to)990-999
Number of pages10
JournalBritish Journal of Anaesthesia
Volume114
Issue number6
Early online date31 Mar 2015
DOIs
Publication statusPublished - Jun 2015

Fingerprint

Selenium
Zinc
Sepsis
Inflammation
Oxidative Stress
Biomarkers
Critical Illness
Interleukin-6
Proteins
Trace Elements
Glutathione Peroxidase
Endothelial Cells
Antioxidants
Lipids

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antioxidants
  • Cells, Cultured
  • Critical Illness
  • Endothelial Cells
  • Female
  • Glutathione Peroxidase
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation
  • Interleukin-6
  • Male
  • Middle Aged
  • Mitochondria
  • Oxidative Stress
  • Selenium
  • Sepsis
  • Young Adult
  • Zinc

Cite this

Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation. / Mertens, K; Lowes, D A; Webster, N R; Talib, J; Hall, L; Davies, M J; Beattie, J H; Galley, H F.

In: British Journal of Anaesthesia, Vol. 114, No. 6, 06.2015, p. 990-999.

Research output: Contribution to journalArticle

Mertens, K ; Lowes, D A ; Webster, N R ; Talib, J ; Hall, L ; Davies, M J ; Beattie, J H ; Galley, H F. / Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation. In: British Journal of Anaesthesia. 2015 ; Vol. 114, No. 6. pp. 990-999.
@article{79c5327b027c4f4c8d07131642825a47,
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.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: registration number NCT01328509.",
keywords = "Adolescent, Adult, Aged, Aged, 80 and over, Antioxidants, Cells, Cultured, Critical Illness, Endothelial Cells, Female, Glutathione Peroxidase, Human Umbilical Vein Endothelial Cells, Humans, Inflammation, Interleukin-6, Male, Middle Aged, Mitochondria, Oxidative Stress, Selenium, Sepsis, Young Adult, Zinc",
author = "K Mertens and Lowes, {D A} and Webster, {N R} and J Talib and L Hall and Davies, {M J} and Beattie, {J H} and Galley, {H F}",
note = "Funding Intensive Care Society and the University of Aberdeen Development Trust. Analyses carried out in Sydney were funded in part by the Australian Research Council through a Centres of Excellence scheme (CE0561607).",
year = "2015",
month = "6",
doi = "10.1093/bja/aev073",
language = "English",
volume = "114",
pages = "990--999",
journal = "British Journal of Anaesthesia",
issn = "0007-0912",
publisher = "ELSEVIER APPL SCI PUBL LTD",
number = "6",

}

TY - JOUR

T1 - Low zinc and selenium concentrations in sepsis are associated with oxidative damage and inflammation

AU - Mertens, K

AU - Lowes, D A

AU - Webster, N R

AU - Talib, J

AU - Hall, L

AU - Davies, M J

AU - Beattie, J H

AU - Galley, H F

N1 - Funding Intensive Care Society and the University of Aberdeen Development Trust. Analyses carried out in Sydney were funded in part by the Australian Research Council through a Centres of Excellence scheme (CE0561607).

PY - 2015/6

Y1 - 2015/6

N2 - 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.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: registration number NCT01328509.

AB - 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.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: registration number NCT01328509.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antioxidants

KW - Cells, Cultured

KW - Critical Illness

KW - Endothelial Cells

KW - Female

KW - Glutathione Peroxidase

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Inflammation

KW - Interleukin-6

KW - Male

KW - Middle Aged

KW - Mitochondria

KW - Oxidative Stress

KW - Selenium

KW - Sepsis

KW - Young Adult

KW - Zinc

U2 - 10.1093/bja/aev073

DO - 10.1093/bja/aev073

M3 - Article

VL - 114

SP - 990

EP - 999

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

IS - 6

ER -