紫外線B波照射による皮膚障害とその予防・治療 —γ-Tocopherol誘導体塗布の効果—

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 γ-tocopherol (γ-Toc) derivative, γ-tocopherol-N,N-dimethylglycinate hydrochloride (γ-TDMG), could protect against UV-induced skin damage. Topical pre- or postapplication of γ-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 E2 (PGE2) levels seen after UV exposure were significantly suppressed by pre- or posttreatment with γ-TDMG. The increase in COX-2 activity was significantly inhibited by γ-TDMG, suggesting that the reduction in PGE2 concentration was due to the direct inhibition of COX-2 activity by γ-TDMG. The derivative strongly inhibited inducible nitric oxide synthase mRNA expression and nitric oxide production. With the application of γ-TDMG, the pigmentation in melanocytes was lightened and the increase melanin concentration was suppressed. γ-TDMG is converted to γ-Toc in the skin and has higher bioavailability than γ-Toc itself. These results suggest that γ-TDMG-derived γ-Toc acts as an antioxidant, antiinflammatory and antipigmentation agent. Our data further suggest that the topical application of γ-TDMG may be efficacious in preventing and reducing UV-induced skin damage in humans.