Biol. Pharm. Bull. 30(4) 692—697 (2007)

various inflammatory skin disorders, skin cancer formation, phototoxicity, and skin aging. ROS can oxidize cellular constituents, leading to the formation of oxidized products such as 8-hydroxyguanosine, lipid hydroperoxides, and protein carbonyls. Skin cells are protected against oxidative injury by a variety of antioxidative components such as copper–zinc superoxide dismutase (Cu, Zn SOD), manganese SOD (Mn SOD), catalase (CAT), and small antioxidant molecules including GSH. However, if the presence of ROS overwhelms the antioxidative capacity of the skin, cellular constituents can be seriously damaged. Indeed, it has been suggested that photoaging might result from imperfect protection against the cumulative stresses of free radicals produced by chronic and repeated UV irradiation. It has been demonstrated that, when exposed to UV radiation, levels of a-tocopherol, ascorbate, and glutathione in the skin are depleted. It has also been reported that the activity of catalase and the levels of nonenzymic antioxidants decrease in photoaged and aged human skin. Thus, the fortification of endogenous antioxidant defense mechanisms may offer a good strategy for the protection of skin against oxidative insults. Fructose-1,6-diphosphate (FDP), a glycolytic metabolite, has been reported to have cytoprotective effects against ischemia and post-ischemic reperfusion injury in the brain and heart, presumably by augmenting anaerobic carbohydrate metabolism. In addition, it has been demonstrated that FDP significantly inhibits generation of oxygen free radicals by stimulated neutrophils and mitigates the adverse effects of endotoxins by regulating the generation of nitric oxide. Recently, we showed that FDP reduced the UVB-induced increase in cellular ROS levels in HaCaT keratinocytes. Although it did not show a direct radical scavenging effect, FDP preserved the antioxidant capacity, including CAT activity and GSH content, in irradiated keratinocytes, implicating its possible application for reducing UVB-induced skin disorders. Since systemic delivery of antioxidants to the skin is generally inefficient, topical application would be advantageous if sufficient penetration is ensured. In this study, we have tested whether topically administered FDP could penetrate into the skin and attenuate UVB-induced oxidative stress in hairless mouse skin.