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A Topical Mitochondria-Targeted Redox Cycling Nitroxide Mitigates Oxidative Stress Induced Skin Damage
- Publication Year :
- 2016
-
Abstract
- Skin is the largest human organ, and it provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation-induced skin damage ranges from photoaging and cutaneous carcinogenesis caused by UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation-induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species. Mitochondria are particularly susceptible to oxidative stress, and mitochondrial-dependent apoptosis plays a major role in radiation-induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent reactive oxygen species accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrially targeted antioxidant prevents and mitigates radiation-induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin's antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress.
- Subjects :
- 0301 basic medicine
Keratinocytes
Antioxidant
medicine.medical_treatment
Photoaging
Human skin
Apoptosis
Dermatology
Mitochondrion
Protein oxidation
medicine.disease_cause
Nitric Oxide
Biochemistry
Skin Diseases
Article
Antioxidants
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Animals
Humans
Molecular Biology
Skin
chemistry.chemical_classification
Inflammation
Reactive oxygen species
Environmental stressor
Electron Spin Resonance Spectroscopy
Cell Biology
medicine.disease
Cell biology
Mitochondria
Mice, Inbred C57BL
Oxidative Stress
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Collagen
Reactive Oxygen Species
Oxidation-Reduction
Oxidative stress
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....0670d1ef152f1cf963b0473fb39c3363