1. ¹Department of Molecular Physiology, Kyoritsu University of Pharmacy, Tokyo, Japan
2. ²Faculty of Pharmaceutical Science, Fukuoka University, Fukuoka, Japan

Correspondence: Dr Shizuko Kobayashi, Kyoritsu University of Pharmacy, Molecular Physiology, Shibakoen 1-5-30, Minato-ku, Tokyo 105-8512, Japan. E-mail: kobayashi-sz@kyoritsu-ph.ac.jp

Received 21 September 2005; Revised 26 December 2005; Accepted 24 January 2006; Published online 16 March 2006.

Abstract

We previously demonstrated that a novel hydrophilic -tocopherol (-Toc) derivative, -tocopherol-N,N-dimethylglycinate hydrochloride (-TDMG) converts to -Toc in the mouse skin and has a higher bioavailability than -Toc itself. In the present study, we determined whether -TDMG could reduce photo-inflammation in mouse skin, and compared its effectiveness to that of -Toc acetate (-TA). Topical pre- or post-application of 5% -TDMG significantly reduced the formation of edema and tempered the increase in cyclooxygenase-2 (COX-2)-catalyzed synthesis of prostaglandin E₂ (PGE₂) that were induced by a single dose of UV irradiation of 2 kJ/m² (290–380 nm, maximum 312 nm). The pre-treatment of mouse skin with 10% -TA had the same anti-inflammatory effect as did -TDMG. In spite of same having the ability to reduce PGE₂ levels, the effect of -TDMG pre-treatment on the inhibition of COX-2 mRNA/protein expression was less than that seen with 10% -TA. In contrast, the increase in COX-2 activity seen after UV exposure was reduced more by -TDMG than by -TA, suggesting that the reduction in PGE₂ levels might have been due to the direct inhibition of COX-2 activity by -TDMG-derived -Toc. Both Toc derivatives strongly suppressed inducible nitric oxide synthase (iNOS) mRNA expression and nitric oxide (NO) production, both of which play important roles in UV-induced inflammation. Both derivatives also significantly reduced lipid peroxidation in response to UV exposure, though -TDMG's ability in this regard was less than that seen with -TA, which correlated with their abilities to suppress COX-2 expression. Thus, the -TDMG-derived -Toc acts as an antioxidant, suppresses iNOS expression and directly inhibits COX-2 activity, all of which likely play a role in mediating its suppressive effects on photo-inflammation. Our data further suggest that the topical application of -TDMG, a novel hydrophilic -Toc derivative, may be efficacious in preventing and reducing UV-induced inflammation in humans.