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.

TitleAntioxidants 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.
Publication TypeJournal Article
Year of Publication2013
AuthorsLowes, DA, Webster, NR, Murphy, MP, Galley, HF
JournalBr J Anaesth
Volume110
Issue3
Pagination472-80
Date Published2013 Mar
ISSN1471-6771
KeywordsAcute Disease, Animals, Antioxidants, Biological Markers, Cytokines, Escherichia coli, Interleukin-6, Kidney Function Tests, Lipopolysaccharides, Liver Function Tests, Male, Melatonin, Mitochondria, Multiple Organ Failure, Organophosphorus Compounds, Oxidative Stress, Oxygen Consumption, Rats, Rats, Sprague-Dawley, Sepsis, Staphylococcus aureus, Ubiquinone
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

CONCLUSIONS: Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis.

DOI10.1093/bja/aes577
Alternate JournalBr J Anaesth
Citation Key10.1093/bja/aes577
PubMed ID23381720
PubMed Central IDPMC3570068
Grant ListG0800149 / / Medical Research Council / United Kingdom
MC_U105663142 / / Medical Research Council / United Kingdom