[UVB-induced skin damage and the protection/treatment--effects of a novel, hydrophilic gamma-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 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.
Kobayashi
Shizuko
S
Molecular Physiology, Kyoritsu University of Pharmacology, Tokyo, Japan. kobayashi-sz@kyoritsu-ph.ac.jp
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D003864:Depression, Chemical; D015232:Dinoprostone / Q000096:biosynthesis; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D012871:Skin Diseases / Q000209:etiology* / Q000517:prevention & control*; D012880:Skin Pigmentation / Q000187:drug effects; D012995:Solubility; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014867:Water; D024504:gamma-Tocopherol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; C512054:gamma-tocopherol-N,N-dimethylglycinate hydrochloride; D014867:Water; D009569:Nitric Oxide; D024504:gamma-Tocopherol; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone; D005998:Glycine