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.
authors: Academic Unit of Anaesthesia and Intensive Care,  School of Medicine and Dentistry, University of Aberdeen, Aberdeen,  UK.
authors: D A
authors: DA
authors: Lowes
authors: N R
authors: NR
authors: Webster
authors: M P
authors: MP
authors: Murphy
authors: H F
authors: HF
authors: Galley
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers; D016207:Cytokines / Q000096:biosynthesis; D004926:Escherichia coli; D015850:Interleukin-6 / Q000378:metabolism*; D007677:Kidney Function Tests; D008070:Lipopolysaccharides; D008111:Liver Function Tests; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use; D008928:Mitochondria / Q000187:drug effects*; D009102:Multiple Organ Failure / Q000503:physiopathology / Q000517:prevention & control; D009943:Organophosphorus Compounds / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D013211:Staphylococcus aureus; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009943:Organophosphorus Compounds; D014451:Ubiquinone; C429014:mitoquinone; D008550:Melatonin
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