Nitroxides and a nitroxide-based UV filter have the potential to photoprotect UVA-irradiated human skin fibroblasts against oxidative damage

Background: Antioxidants are now being incorporated into sunscreens as additional topical measure for delaying the aging process and reducing photo-damage to skin induced by excessive UVA exposure. UVA radiation reaching the skin leads to the generation of ROS (reactive oxygen species) implicated in DNA damage and activation of matrix metalloproteinase-1 (MMP-1) responsible for collagen damage and photo-aging. Nitroxides are a class of compounds endowed with versatile antioxidant activity and recently, nitroxide-based UV filters in which a nitroxide moiety has been attached to the most popular UV filter present in sunscreens have been developed. Objective: This study explores the potential photo-protective effects of these compounds on ROS production and induction of MMP-1 in cultured human dermal fibroblasts exposed to UVA. For comparison, vitamin E was also tested. Methods: The effects were assessed by measuring intracellular ROS production using a ROS-index probe and MMP-1 mRNA expression levels using quantitative real-time PCR (qPCR). Results: Exposure of fibroblasts to 18 J/cm(2) UVA lead to a two-fold increase in ROS production which was reduced to non-irradiated control levels in the presence of 50 mu M nitroxide compounds and vitamin E. Under the same conditions, a ten-fold increase in MMP-1 mRNA expression levels was observed 24 h post-UVA treatment which was significantly reduced by all nitroxide compounds but not vitamin E. Conclusion: The results of this study support the potential use of nitroxide compounds, including novel nitroxide-based UV filters, as a useful and alternative strategy for improving the efficacy of topical formulations against photo-aging and possibly photo-carcinogenesis. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.