Abstract
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 language | English |
|---|---|
| Pages (from-to) | 472-480 |
| Number of pages | 9 |
| Journal | British Journal of Anaesthesia |
| Volume | 110 |
| Issue number | 3 |
| Early online date | 4 Feb 2013 |
| DOIs | |
| Publication status | Published - 1 Mar 2013 |
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Keywords
- co-enzyme Q10
- interleukin-6
- interleukin-10
- melatonin
- sepsis
- tocopherol
Cite this
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. / Lowes, D. A.; Webster, N. R.; Murphy, M. P.; Galley, H. F.
In: British Journal of Anaesthesia, Vol. 110, No. 3, 01.03.2013, p. 472-480.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=84874355329&partnerID=8YFLogxK
U2 - 10.1093/bja/aes577
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
IS - 3
ER -