UVB-induced skin damage and the protection/treatment -: effects of a novel, hydrophilic γ-tocopherol derivative

Ultraviolet radiation is the major environmental cause of skin damage. Although only 0.5% of ultraviolet B (UVB) radiation reaches the earth, it is the main cause of sunburn and inflammation and the most carcinogenic constituent of sunlight. We investigated whether the topical application of a novel, water-soluble gamma-tocopherol (gamma-Toc) derivative, gamma-tocopherol-N,N-dimethylglycinate hydrochloride (gamma-TDMG), could protect against UV-induced skin damage. Topical pre- or postapplication of gamma-TDMG solution significantly prevented sunburn cell formation, lipid peroxidation, and edema/inflammation that were induced by exposure to a single dose of UV irradiation. Cyclooxygenase-2 (COX-2)-catalyzed synthesis of prostaglandin E-2 (PGE(2)) levels seen after UV exposure were significantly suppressed by pre- or posttreatment with gamma-TDMG. The increase in COX-2 activity was significantly inhibited by gamma-TDMG, suggesting that the reduction in PGE2 concentration was due to the direct inhibition of COX-2 activity by gamma-TDMG. The derivative strongly inhibited inducible nitric oxide synthase mRNA expression and nitric oxide production. With the application of gamma-TDMG, the pigmentation in melanocytes was lightened and the increase melanin concentration was suppressed. gamma-TDMG is converted to gamma-Toc in the skin and has higher bioavailability than gamma-Toc itself. These results suggest that gamma-TDMG-derived gamma-Toc acts as an antioxidant, antiinflammatory and antipigmentation agent. Our data further suggest that the topical application of gamma-TDMG may be efficacious in preventing and reducing UV-induced skin damage in humans.