Topical Application of a Novel, Water‐soluble γ‐Tocopherol Derivative Prevents UV‐induced Skin Damage in Mice¶

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ABSTRACTWe investigated whether the topical application of a novel, water‐soluble γ‐tocopherol (γ‐Toc) derivative, γ‐tocopherol‐N,N‐dimethylglycinate hydrochloride (γ‐TDMG), could protect against UV‐induced skin damage in hairless mice. Topical pre‐or post‐application of a 5% (93 mM) γ‐TDMG solution in water/propylene glycol/ethanol (2:1:2) significantly prevented sunburn cell formation, lipid peroxidation and edema/inflammation that were induced by exposure to a single dose of UV irradiation of 5 kJ/m2 (290–380 nm, maximum 312 nm). This effect was greater than that seen with two α‐Toc derivatives, α‐tocopherol acetate (α‐TA) and α‐tocopherol‐N,N‐dimethylglycinate (α‐TDMG). When a 5% solution of γ‐TDMG was applied to mouse skin for 1 h, cutaneous γ‐Toc increased by 25‐fold after 24 h; levels of cutaneous α‐Toc increased by only two‐and eight‐fold in α‐TDMG and α‐TA treated skins, respectively. These findings indicated that γ‐TDMG immediately converted to γ‐Toc in the skin and suggest that ability of γ‐TDMG to protect the skin from the damaging effects of irradiation was due to its conversion to γ‐Toc. When a 5% solution of γ‐Toc was applied to mouse skin for 1 h, cutaneous γ‐Toc rapidly increased by 25‐fold, but fell to baseline levels by 24 h. In contrast, the concentration of γ‐Toc in skin that was treated with γ‐TDMG similarly increased, but these high levels were maintained after 24 h. These results suggest that γ‐TDMG may be a more effective source of γ‐Toc in skin. Thus, the topical application of γ‐TDMG may be efficacious for the prevention of UV‐B‐induced skin damage.