Topical application of a novel, hydrophilic gamma-tocopherol derivative reduces photo-inflammation in mice skin.

Abstract

We previously demonstrated that a novel hydrophilic gamma-tocopherol (gamma-Toc) derivative, gamma-tocopherol-N,N-dimethylglycinate hydrochloride (gamma-TDMG) converts to gamma-Toc in the mouse skin and has a higher bioavailability than gamma-Toc itself. In the present study, we determined whether gamma-TDMG could reduce photo-inflammation in mouse skin, and compared its effectiveness to that of alpha-Toc acetate (alpha-TA). Topical pre- or post-application of 5% gamma-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% alpha-TA had the same anti-inflammatory effect as did gamma-TDMG. In spite of same having the ability to reduce PGE2 levels, the effect of gamma-TDMG pre-treatment on the inhibition of COX-2 mRNA/protein expression was less than that seen with 10% alpha-TA. In contrast, the increase in COX-2 activity seen after UV exposure was reduced more by gamma-TDMG than by alpha-TA, suggesting that the reduction in PGE2 levels might have been due to the direct inhibition of COX-2 activity by gamma-TDMG-derived gamma-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 gamma-TDMG's ability in this regard was less than that seen with alpha-TA, which correlated with their abilities to suppress COX-2 expression. Thus, the gamma-TDMG-derived gamma-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 gamma-TDMG, a novel hydrophilic gamma-Toc derivative, may be efficacious in preventing and reducing UV-induced inflammation in humans.

• Authors: Emiko Yoshida, Tatsuya Watanabe, Jiro Takata, Akihiko Yamazaki, Yoshiharu Karube, Shizuko Kobayashi
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 126 Issue 7 Pg. 1633-40 (Jul 2006) ISSN: 0022-202X [Print] United States
• PMID: 16543897 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Cyclooxygenase Inhibitors
• RNA, Messenger
• Reactive Oxygen Species
• gamma-tocopherol-N,N-dimethylglycinate hydrochloride
• Nitric Oxide
• gamma-Tocopherol
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Cyclooxygenase 2
• alpha-Tocopherol
• Dinoprostone
• Tocopherols
• Glycine
• Indomethacin

Topics

• Administration, Topical
• Animals
• Antioxidants (administration & dosage, pharmacology)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase Inhibitors (pharmacology)
• Dinoprostone (metabolism)
• Epidermis (chemistry, pathology, physiopathology, radiation effects)
• Female
• Gene Expression Regulation (drug effects, radiation effects)
• Glycine (administration & dosage, analogs & derivatives, pharmacology)
• Indomethacin (pharmacology)
• Inflammation (drug therapy, etiology)
• Lipid Peroxidation (drug effects, radiation effects)
• Mice
• Mice, Hairless
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• RNA, Messenger (analysis)
• Reactive Oxygen Species (metabolism)
• Tocopherols
• Ultraviolet Rays (adverse effects)
• alpha-Tocopherol (administration & dosage, analogs & derivatives, analysis, pharmacology)
• gamma-Tocopherol (administration & dosage, analogs & derivatives, pharmacology)