Topical application of gamma-tocopherol derivative prevents UV-induced skin pigmentation.
We previously reported that a novel hydrophilic gamma-tocopherol (gamma-Toc) derivative, gamma-tocopheryl-N,N-dimethylglycinate hydrochloride (gamma-TDMG) gets converted to the antioxidant gamma-Toc in skin. We also found that this derivative displayed greater bioavailability than gamma-Toc itself. In the present study, we determined whether gamma-TDMG could reduce UV-induced skin pigmentation in brownish guinea pigs. gamma-TDMG (0.1 or 0.5%) was topically applied to the skin before and after it was exposed to UVB plus UVA (3 times/week for 1 week), and then 10 times/week for 4 weeks thereafter. Treatment with 0.5% gamma-TDMG resulted in significant skin lightening (70% of the pigmentation of irradiated controls). We also found that melanin synthesis was dose-dependently inhibited by gamma-TDMG in murine B16 melanoma cells. When gamma-TDMG or kojic acid (250 microM) were added to homogenates of B16 melanoma cells, their tyrosinase activity was significantly inhibited by approximately 40% and 75%, respectively. Mushroom tyrosinase activity was significantly inhibited by 200 microM gamma-Toc and kojic acid, but not gamma-TDMG. When B16 cells were incubated with 250 microM gamma-TDMG for 24 or 48 h, their intracellular gamma-Toc concentrations rose over 100 fold to 10.5 and 11.2 nmol/10(6) cells, respectively, suggesting that gamma-TDMG was rapidly converted to gamma-Toc in these cells and that their reduced melanin synthesis may have been due to the activity of gamma-Toc. Our data further suggest that the topical application of gamma-TDMG may be efficacious in preventing photo-induced skin pigmentation in humans.
Kuwabara
Yuka
Y
Kyoritsu University of Pharmacy, Tokyo, Japan.
Watanabe
Tatsuya
T
Yasuoka
Shingo
S
Fukui
Kohsuke
K
Takata
Jiro
J
Karube
Yoshiharu
Y
Okamoto
Yuko
Y
Asano
Shin
S
Katoh
Eiko
E
Tsuzuki
Toshi
T
Kobayashi
Shizuko
S
D000287:Administration, Topical; D000818:Animals; D045744:Cell Line, Tumor; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006168:Guinea Pigs; D008543:Melanins / Q000096:biosynthesis*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D012880:Skin Pigmentation / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays; D024504:gamma-Tocopherol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D008543:Melanins; C512054:gamma-tocopherol-N,N-dimethylglycinate hydrochloride; D024504:gamma-Tocopherol; D005998:Glycine