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
PGE(2) 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.