Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice
Abstract
The mitochondria-targeted quinone MitoQ protects mitochondria in animal studies of pathologies in vivo and is being developed as a therapy for humans. However, it is unclear whether the protective action of MitoQ is entirely due to its antioxidant properties, because long-term MitoQ administration may alter whole-body metabolism and gene expression. To address this point, we administered high levels of MitoQ orally to wild-type C57BL/6 mice for up to 28 weeks and investigated the effects on whole-body physiology, metabolism, and gene expression, finding no measurable deleterious effects. In addition, because antioxidants can act as pro-oxidants under certain conditions in vitro, we examined the effects of MitoQ administration on markers of oxidative damage. There were no changes in the expression of mitochondrial or antioxidant genes as assessed by DNA microarray analysis. There were also no increases in oxidative damage to mitochondrial protein, DNA, or cardiolipin, and the activities of mitochondrial enzymes were unchanged. Therefore, MitoQ does not act as a pro-oxidant in vivo. These findings indicate that mitochondria-targeted antioxidants can be safely administered long-term to wild-type mice.
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Concentrations of mitochondrially targeted antioxidants used in vitro are typically 10-100 times greater than those generated from oral dosing in a wide range of animal models and in humans.
“However, concentrations used in vitro are typically 10–100 times greater than those generated from oral dosing in a wide range of animal models and in humans.”
From Mitochondrially targeted compounds and their impact on cellular bioenergetics (2013) · cites this paper as [26]
When administered to wild-type mice for several months, MitoQ has no effect on the function of subsequently isolated mitochondria, mtDNA, nuclear or mitochondrial gene expression, whole-body metabolism, whole-body motor function, or food and liquid consumption.
“When administered to wild-type mice for several months, MitoQ has no effect on the function of subsequently isolated mitochondria, on mtDNA, on nuclear or mitochondrial gene expression, on whole-body metabolism, on whole-body motor function, or on food and liquid consumption (Rodriguez-Cuenca et al., 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 Rodriguez-Cuenca et al., 2010
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- Authors
- Rodriguez-Cuenca, S., Cochemé, H. M., Logan, A., Abakumova, I., Prime, T. A., Rose, C., Vidal-Puig, A., Smith, A. C., Rubinsztein, D. C., Fearnley, I. M., Jones, B. A., Pope, S., Heales, S. J. R., Lam, B. Y. H., Neogi, S. G., McFarlane, I., James, A. M., Smith, R. A. J., & Murphy, M. P.
- Affiliations
- University College London (GB)
- MRC Mitochondrial Biology Unit (GB)
- University of Cambridge (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- NIHR Cambridge Biomedical Research Centre (GB)
- University of Otago (NZ)
- Corresponding author
- Murphy, Michael P.
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 48
- Issue
- 1
- Pages
- 161-172
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2051753090
- Cited by
- 218
- References
- 12
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 10 · 2023: 11 · 2022: 16 · 2021: 13 · 2020: 18 · 2019: 12 · 2018: 11 · 2017: 12 · 2016: 13 · 2015: 16 · 2014: 18 · 2013: 11 · 2012: 13
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (064354)
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- MitoQ, mitochondria-targeted antioxidants, long-term oral administration, pro-oxidant activity, oxidative damage, cardiolipin oxidation, mitochondrial gene expression, whole-body metabolism, drug safety, wild-type mice
- MeSH terms
- Administration, Oral, Animals, Antioxidants, Mice, Inbred C57BL, Mitochondria, Organophosphorus Compounds, Ubiquinone, Oxidative Stress, Oligonucleotide Array Sequence Analysis, Mice
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