Skin cell protection against UVA by Sideroxyl, a new antioxidant complementary to sunscreens.
Oxidative stress resulting from photosensitized ROS production in skin is widely accepted as the main contributor to the deleterious effects of UVA exposure. Among the mechanisms known to be involved in UVA-induced oxidative damage, iron plays a central role. UVA radiation of skin cells induces an immediate release of iron, which can then act as a catalyst for uncontrolled oxidation reactions of cell components. Such site-specific damage can scarcely be counteracted by classical antioxidants. In contrast, iron chelators potentially offer an effective way to protect skin against UVA insults. However, iron chelation is very difficult to achieve without disturbing iron homeostasis or inducing iron depletion. A novel compound was developed to avoid these potentially harmful side effects. Sideroxyl was designed to acquire its strong chelating capability only during oxidative stress according to an original process of intramolecular hydroxylation. Herein, we describe in vitro results demonstrating the protective efficiency of Sideroxyl against deleterious effects of UVA at the molecular, cellular, and tissular levels. First, the Sideroxyl diacid form protects a model protein against UVA-induced photosensitized carbonylation. Second, intracellular ROS are dose-dependently decreased in the presence of Sideroxyl in both human cultured fibroblasts and human keratinocytes. Third, Sideroxyl protects normal human fibroblasts against UVA-induced DNA damage as measured by the comet assay and MMP-1 production. Finally, Sideroxyl provides protection against UVA-induced alterations in human reconstructed skin. These results suggest that Sideroxyl may prevent UVA-induced damage in human skin as a complement to sunscreens, especially in the long-wavelength UVA range.
Pygmalion
Marie-Jocelyne
MJ
L'Oréal Advanced Research, 93600 Aulnay sous bois, France.
Ruiz
Laetitia
L
Popovic
Evelyne
E
Gizard
Julie
J
Portes
Pascal
P
Marat
Xavier
X
Lucet-Levannier
Karine
K
Muller
Benoit
B
Galey
Jean-Baptiste
JB
D000975:Antioxidants / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004817:Epidermis / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D007501:Iron / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D012710:Serum Albumin, Bovine / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D013473:Sunscreening Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000975:Antioxidants; C556050:Sideroxyl; D013473:Sunscreening Agents; D012710:Serum Albumin, Bovine; D004492:Edetic Acid; D007501:Iron