The mitochondria-targeted antioxidant MitoQ protects against organ damage in a lipopolysaccharide–peptidoglycan model of sepsis
Abstract
Sepsis is characterised by a systemic dysregulated inflammatory response and oxidative stress, often leading to organ failure and death. Development of organ dysfunction associated with sepsis is now accepted to be due at least in part to oxidative damage to mitochondria. MitoQ is an antioxidant selectively targeted to mitochondria that protects mitochondria from oxidative damage and which has been shown to decrease mitochondrial damage in animal models of oxidative stress. We hypothesised that if oxidative damage to mitochondria does play a significant role in sepsis-induced organ failure, then MitoQ should modulate inflammatory responses, reduce mitochondrial oxidative damage, and thereby ameliorate organ damage. To assess this, we investigated the effects of MitoQ in vitro in an endothelial cell model of sepsis and in vivo in a rat model of sepsis. In vitro MitoQ decreased oxidative stress and protected mitochondria from damage as indicated by a lower rate of reactive oxygen species formation (P=0.01) and by maintenance of the mitochondrial membrane potential (P<0.005). MitoQ also suppressed proinflammatory cytokine release from the cells (P<0.05) while the production of the anti-inflammatory cytokine interleukin-10 was increased by MitoQ (P<0.001). In a lipopolysaccharide-peptidoglycan rat model of the organ dysfunction that occurs during sepsis, MitoQ treatment resulted in lower levels of biochemical markers of acute liver and renal dysfunction (P<0.05), and mitochondria…
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When MitoQ is administered to in vivo animal models of pathologies, it reduces both oxidative damage and the pathologies.
“A number of studies show that, when MitoQ is administered to in vivo animal models of pathologies, it reduces both oxidative damage and the pathologies (Adlam et al., 2005; Lowes et al., 2008; Graham et al., 2009; Supinski et al., 2009; Chacko et al., 2010; Smith and Murphy 2010).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Lowes et al., 2008
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- Authors
- Lowes, D. A., Thottakam, B. M. V., Webster, N. R., Murphy, M. P., & Galley, H. F.
- Affiliations
- University of Aberdeen (GB)
- MRC Mitochondrial Biology Unit (GB)
- Corresponding author
- Galley, Helen F.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 45
- Issue
- 11
- Pages
- 1559-1565
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2121393443
- Cited by
- 261
- References
- 6
- Citations by year
- 2026: 4 · 2025: 16 · 2024: 12 · 2023: 12 · 2022: 14 · 2021: 16 · 2020: 18 · 2019: 10 · 2018: 20 · 2017: 13 · 2016: 11 · 2015: 14 · 2014: 19 · 2013: 17 · 2012: 17
- FWCI
- 11.63
- Type
- journal article
- Language
- en
- Update notices
- erratum (2009-10-01)
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- MitoQ, sepsis, mitochondria-targeted antioxidants, mitochondrial oxidative damage, organ dysfunction, endothelial cells, reactive oxygen species, mitochondrial membrane potential, inflammatory cytokines, IL-10, liver dysfunction, renal dysfunction, oxidative stress
- MeSH terms
- Animals, Antioxidants, Cell Line, Creatinine, Disease Models, Animal, Humans, Lipopolysaccharides, Mitochondria, Organophosphorus Compounds, Peptidoglycan, Spectrometry, Fluorescence, Ubiquinone, Cytokines, Interleukin-10, Reactive Oxygen Species, Oxidative Stress, Sepsis, Endothelial Cells, Rats, Membrane Potential, Mitochondrial
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