Topical application of gamma-tocopherol derivative prevents UV-induced skin pigmentation.

Abstract

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.

• Authors: Yuka Kuwabara, Tatsuya Watanabe, Shingo Yasuoka, Kohsuke Fukui, Jiro Takata, Yoshiharu Karube, Yuko Okamoto, Shin Asano, Eiko Katoh, Toshi Tsuzuki, Shizuko Kobayashi
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 29 Issue 6 Pg. 1175-9 (Jun 2006) ISSN: 1347-5215 [Electronic] Japan
• PMID: 16755012 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Melanins
• gamma-tocopherol-N,N-dimethylglycinate hydrochloride
• gamma-Tocopherol
• Glycine

Topics

• Administration, Topical
• Animals
• Cell Line, Tumor
• Glycine (administration & dosage, analogs & derivatives, therapeutic use)
• Guinea Pigs
• Melanins (biosynthesis)
• Skin (drug effects, metabolism, radiation effects)
• Skin Pigmentation (drug effects, radiation effects)
• Ultraviolet Rays
• gamma-Tocopherol (administration & dosage, analogs & derivatives, therapeutic use)