Free Radical Biology and Medicine

Volume 85, August 2015, Pages 1–11

Original Contribution

Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcinogenesis

• J. Antoni Sirerol^a,
• Fatima Feddi^b,
• Salvador Mena^a,
• María L. Rodriguez^a,
• Paula Sirera^a,
• Miguel Aupí^a,
• Salvador Pérez^a,
• Miguel Asensi^{a, b},
• Angel Ortega^{a, b},
• José M. Estrela^{a, b, ,}

doi:10.1016/j.freeradbiomed.2015.03.027

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Highlights

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Pter and Resv prevent acute UVB radiation-induced inflammation and photoaging.

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Pter, but not Resv, prevents chronic UVB radiation-induced carcinogenesis.

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Pter decreases chronic UVB radiation-induced oxidative damage, potentially via modulation of Nrf2 activity.

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Abstract

The aim of our study was to investigate in the SKH-1 hairless mouse model the effect of pterostilbene (Pter), a natural dimethoxy analog of resveratrol (Resv), against procarcinogenic ultraviolet B radiation (UVB)-induced skin damage. Pter prevented acute UVB (360 mJ/cm²)-induced increase in skin fold, thickness, and redness, as well as photoaging-associated skin wrinkling and hyperplasia. Pter, but not Resv, effectively prevented chronic UVB (180 mJ/cm², three doses/week for 6 months)-induced skin carcinogenesis (90% of Pter-treated mice did not develop skin carcinomas, whereas a large number of tumors were observed in all controls). This anticarcinogenic effect was associated with (a) maintenance of skin antioxidant defenses (i.e., glutathione (GSH) levels, catalase, superoxide, and GSH peroxidase activities) close to control values (untreated mice) and (b) an inhibition of UVB-induced oxidative damage (using as biomarkers 8-hydroxy-2′-deoxyguanosine, protein carbonyls, and isoprostanes). The molecular mechanism underlying the photoprotective effect elicited by Pter was further evaluated using HaCaT immortalized human keratinocytes and was shown to involve potential modulation of the Nrf2-dependent antioxidant response.

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Graphical abstract

Abbreviations

• Pter, pterostilbene;
• Resv, resveratrol;
• GSH, glutathione;
• PMMA, polymethylmethacrylate;
• SPF, sun protection factor;
• CAT, catalase;
• SOD, superoxide dismutase;
• GPX, glutathione peroxidase;
• Nrf2, nuclear factor erythroid-2-related factor-2;
• γ-GCL, γ-glutamate–cysteine ligase;
• Trx, thioredoxin;
• ROS, reactive oxygen species;
• DFO, desferrioxamine;
• DFP, deferiprone

Keywords

• Phytochemicals;
• Polyphenols;
• Stilbenes;
• Pterostilbene;
• Resveratrol;
• UV radiation;
• Photocarcinogenesis;
• Skin damage;
• Oxidative stress;
• Free radicals

Corresponding author at: Department of Physiology, University of Valencia, 46010 Valencia, Spain. Fax: +34 963864642.

Copyright © 2015 Elsevier Inc. All rights reserved.