Protective effects of a comprehensive topical antioxidant against ozone-induced damage in a reconstructed human skin model.

Tropospheric ozone (O) is a source of oxidative stress. This study examined the ability of a topical antioxidant (WEL-DS) to inhibit O-mediated damage in a human epidermal skin model. Four groups of tissues (N = 24) were compared: Group 1 (control) were untreated and unexposed; Group 2 were untreated and exposed to O (0.4 ppm, 4 h); Group 3 were pretreated with WEL-DS and unexposed; Group 4 were pretreated with WEL-DS and exposed to O (0.4 ppm, 4 h). Pretreated tissues were topically treated with 20 uL of WEL-DS and incubated for up to 20 h at 37 °C [humidified, 5% carbon dioxide (CO)]. After 24 h, tissues were re-treated with WEL-DS and exposed to O Tissues were evaluated for Reactive Oxygen Species (ROS), hydrogen peroxide (HO), 4-hydroxynonenal (4-HNE) protein adducts, NF-κB p65 response and histology. In O-exposed groups, WEL-DS significantly inhibited ROS formation vs. untreated tissues (p < 0.05). Pretreatment with WEL-DS inhibited HO production vs. untreated tissues (p < 0.05), and decreased NF-κB p65 transcription factor signal. Oxidative stress induction in O-exposed tissues was confirmed by increased levels of 4-HNE protein adducts (marker of lipid peroxidation); WEL-DS application reduced this effect. WEL-DS inhibited damage in tissues exposed to O with no significant changes in epidermal structure. A comprehensive topical antioxidant significantly diminished O-induced oxidative damage in a human epidermal skin model.