Comparing the effects of mitochondrial targeted and localized antioxidants with cellular antioxidants in human skin cells exposed to UVA and hydrogen peroxide
Abstract
Skin cancer and aging are linked to increased cellular reactive oxygen species (ROS), particularly following exposure to ultraviolet A (UVA) in sunlight. As mitochondria are the main source of cellular ROS, this study compared the protective effects of mitochondria-targeted and -localized antioxidants (MitoQ and tiron, respectively) with cellular antioxidants against oxidative stress-induced [UVA and hydrogen peroxide (H2O2)] mitochondrial DNA (mtDNA) damage in human dermal fibroblasts. With the use of a long quantitative PCR assay, tiron (EC50 10 mM) was found to confer complete (100%) protection (P<0.001) against both UVA- and H2O2-induced mtDNA damage, whereas MitoQ (EC50 750 nM) provided less protection (17 and 32%, respectively; P<0.05). This particular protective effect of tiron was greater than a range of cellular antioxidants investigated. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway provides cellular protection against oxidative stress. An ELISA assay for the Nrf2 target gene heme oxygenase-1 (HO-1) and studies using Nrf2 small interfering RNA both indicated that tiron's mode of action was Nrf2 independent. The comet assay showed that tiron's protective effect against H2O2-induced nuclear DNA damage was greater than the cellular antioxidants and MitoQ (P<0.001). This study provides a platform to investigate molecules with similar structure to tiron as potent and clinically relevant antioxidants.
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Tiron, an antioxidant preferentially localised to the mitochondria, was able to confer complete protection against UVA- and H2O2-induced mitochondrial damage.
“A study comparing the effects of mitochondria-localised antioxidants with cellular antioxidants found that tiron, an antioxidant preferentially localised to the mitochondria, was able to confer complete protection against UVA-and H 2 O 2 -induced mitochondrial damage [47].”
From Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin (2017) · cites this paper as [47]
The protective effect of tiron was greater than a range of cellular antioxidants investigated, including resveratrol and curcumin.
“Interestingly, the protective effect of tiron was found to be greater than a range of cellular antioxidants investigated, which included resveratrol and curcumin.”
From Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin (2017) · cites this paper as [47]
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- Authors
- Oyewole, A. O., Wilmot, M., Fowler, M., & Birch‐Machin, M. A.
- Affiliations
- Newcastle University (GB)
- Unilever (United Kingdom) (GB)
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2013-10-10
- Volume
- 28
- Issue
- 1
- Pages
- 485-494
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2138631058
- Cited by
- 90
- References
- 72
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 11 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 5 · 2016: 12 · 2015: 11 · 2014: 5
- FWCI
- 10.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- mitochondria-targeted antioxidants, MitoQ, Tiron, hydrogen peroxide, mitochondrial DNA damage, reactive oxygen species, dermal fibroblasts, Nrf2 signaling, heme oxygenase-1, nuclear DNA damage, skin aging, skin cancer
- MeSH terms
- Antioxidants, DNA Damage, Humans, Hydrogen Peroxide, Mitochondria, Organophosphorus Compounds, Skin, 1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt, Ubiquinone, Ultraviolet Rays, Comet Assay
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