title: Skin cell protection against UVA by Sideroxyl, a new antioxidant complementary to sunscreens.
abstract: 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.
authors.affiliation: L'Oréal Advanced Research, 93600 Aulnay sous bois, France.
authors.forename: Marie-Jocelyne
authors.initials: MJ
authors.lastname: Pygmalion
authors.forename: Laetitia
authors.initials: L
authors.lastname: Ruiz
authors.forename: Evelyne
authors.initials: E
authors.lastname: Popovic
authors.forename: Julie
authors.initials: J
authors.lastname: Gizard
authors.forename: Pascal
authors.initials: P
authors.lastname: Portes
authors.forename: Xavier
authors.initials: X
authors.lastname: Marat
authors.forename: Karine
authors.initials: K
authors.lastname: Lucet-Levannier
authors.forename: Benoit
authors.initials: B
authors.lastname: Muller
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Galey
mesh_terms: 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*
chemical_list: D000975:Antioxidants; C556050:Sideroxyl; D013473:Sunscreening Agents; D012710:Serum Albumin, Bovine; D004492:Edetic Acid; D007501:Iron