Cited by 90Skin Protection and AgingMitochondrial Function and PathologyGenomics, phytochemicals, and oxidative stress

Comparing the effects of mitochondrial targeted and localized antioxidants with cellular antioxidants in human skin cells exposed to UVA and hydrogen peroxide

Oyewole, Anne O., Wilmot, Marie‐Claire, Fowler, Mark, Birch‐Machin, Mark A.·2014·The FASEB Journal

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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Registry

Crossref · 10.1096/fj.13-237008

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72 of 72 references verified0 citation errors · 0 not checkable

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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].”
  • 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.”

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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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