+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

A Topical Mitochondria-Targeted Redox-Cycling Nitroxide Mitigates Oxidative Stress-Induced Skin Damage

A Topical Mitochondria-Targeted Redox-Cycling Nitroxide Mitigates Oxidative Stress-Induced Skin Damage

Journal of Investigative Dermatology 137(3): 576-586

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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 057047631

Download citation: RISBibTeXText

PMID: 27794421

DOI: 10.1016/j.jid.2016.09.033

Related references

Topical Application of GS-Nitroxide JP4-039 Emulsion Mitigates Ionizing Irradiation Induced Skin Burns. International Journal of Radiation Oncology*biology*physics 78(3): S634-S635, 2010

Oxidative stress induced by redox cycling of salsolinol leads to DNA damage and cell death. Journal of Neurochemistry 70(Suppl. 2): S62, 1998

Mitochondria-targeted redox probes as tools in the study of oxidative damage and ageing. Mechanisms of Ageing and Development 126(9): 982-986, 2005

The mitochondria targeted antioxidant MitoQ protects against fluoroquinolone-induced oxidative stress and mitochondrial membrane damage in human Achilles tendon cells. Free Radical Research 43(4): 323-328, 2009

Mitochondria-targeted cytochrome P450 2E1 induces oxidative damage and augments alcohol-mediated oxidative stress. Journal of Biological Chemistry 285(32): 24609-24619, 2010

MitoVitE, a mitochondria-targeted antioxidant, limits paclitaxel-induced oxidative stress and mitochondrial damage in vitro, and paclitaxel-induced mechanical hypersensitivity in a rat pain model. British Journal of Anaesthesia 117(5): 659-666, 2016

Bidentate nitroxide ligands stable toward oxidative redox cycling and their complexes with cerium and lanthanum. Chemical Communications 51(81): 15047-15050, 2015

Grape seed and skin extract mitigates garlic-induced oxidative stress in rat liver. Canadian Journal of Physiology and Pharmacology 90(5): 547-556, 2012

Lysosomal oxidative stress cytotoxicity induced by nitrofurantoin redox cycling in hepatocytes. Advances in Experimental Medicine and Biology 500: 261-265, 2001

Oxidative DNA damage and cytotoxicity induced by copper-stimulated redox cycling of salsolinol, a neurotoxic tetrahydroisoquinoline alkaloid. Free Radical Biology & Medicine 30(12): 1407-1417, 2001

Potentially Lethal Damage Repair is Enhanced by the Mitochondria-targeted Nitroxide JP4-039. International Journal of Radiation Oncology*biology*physics 75(3): S550-S551, 2009

Grape seed and skin extract mitigates heart and liver oxidative damage induced by a high-fat diet in the rat: gender dependency. Canadian Journal of Physiology and Pharmacology 91(12): 1076-1085, 2013

Diphenyleneiodonium Mitigates Bupivacaine-Induced Sciatic Nerve Damage in a Diabetic Neuropathy Rat Model by Attenuating Oxidative Stress. Anesthesia and Analgesia 125(2): 653-661, 2017

Aminoguanidine mitigates apoptosis, testicular seminiferous tubules damage, and oxidative stress in streptozotocin-induced diabetic rats. Tissue and Cell 47(3): 284-290, 2015

Trans-chalcone added in topical formulation inhibits skin inflammation and oxidative stress in a model of ultraviolet B radiation skin damage in hairless mice. Journal of Photochemistry and Photobiology. B Biology 171: 139-146, 2017