Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

D. A. Lowes, N. R. Webster, M. P. Murphy, H. F. Galley

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Abstract

Background: Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage.

Methods: Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines.

Results: MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001).

Conclusions: Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.
Original languageEnglish
Pages (from-to)472-480
Number of pages9
JournalBritish Journal of Anaesthesia
Volume110
Issue number3
Early online date4 Feb 2013
DOIs
Publication statusPublished - 1 Mar 2013

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Interleukin-6
Sepsis
Mitochondria
Oxidative Stress
Antioxidants
Biomarkers
Melatonin
Peptidoglycan
Lipopolysaccharides
Critical Care
Transferases
Alanine
Cause of Death
Creatinine
Respiration
Cytokines
Inflammation
Therapeutics

Keywords

  • co-enzyme Q10
  • interleukin-6
  • interleukin-10
  • melatonin
  • sepsis
  • tocopherol

Cite this

@article{54a6aebe3dcb4991a782786c5884629b,
title = "Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis",
abstract = "Background: Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage.Methods: Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines.Results: MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001).Conclusions: Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.",
keywords = "co-enzyme Q10, interleukin-6, interleukin-10, melatonin, sepsis, tocopherol",
author = "Lowes, {D. A.} and Webster, {N. R.} and Murphy, {M. P.} and Galley, {H. F.}",
note = "Funding This study was funded by the Medical Research Council (Grant number G0800149). Research material from this study is not available. Acknowledgement We are very grateful to Dr Robin A.J. Smith, Department of Chemistry, University of Otago, Dunedin, New Zealand, for the generous gifts of MitoE and MitoQ, without which this work would not have been possible.",
year = "2013",
month = "3",
day = "1",
doi = "10.1093/bja/aes577",
language = "English",
volume = "110",
pages = "472--480",
journal = "British Journal of Anaesthesia",
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}

TY - JOUR

T1 - Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

AU - Lowes, D. A.

AU - Webster, N. R.

AU - Murphy, M. P.

AU - Galley, H. F.

N1 - Funding This study was funded by the Medical Research Council (Grant number G0800149). Research material from this study is not available. Acknowledgement We are very grateful to Dr Robin A.J. Smith, Department of Chemistry, University of Otago, Dunedin, New Zealand, for the generous gifts of MitoE and MitoQ, without which this work would not have been possible.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - Background: Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage.Methods: Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines.Results: MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001).Conclusions: Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.

AB - Background: Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage.Methods: Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines.Results: MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001).Conclusions: Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.

KW - co-enzyme Q10

KW - interleukin-6

KW - interleukin-10

KW - melatonin

KW - sepsis

KW - tocopherol

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DO - 10.1093/bja/aes577

M3 - Article

C2 - 23381720

VL - 110

SP - 472

EP - 480

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

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