We investigated the antioxidative activities and the effects on acute inflammation in mice of a novel diaminouracil derivative, CX-659S ((S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3- methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione). CX-659S showed potent scavenging activities against the hydroxyl radical and peroxynitrite and inhibited lipid peroxidation in rat brain homogenates in vitro. Topically applied CX-659S dose-dependently inhibited arachidonic acid- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. Consistent with its antioxidative properties in vitro, CX-659S dramatically attenuated the accumulation of lipid peroxides in the mouse ear elicited by repeated application of TPA. Previously, we reported the effectiveness of CX-659S against contact hypersensitivity reactions in both mouse and guinea pig models. These present results further suggest the therapeutic potential of CX-659S for acute skin inflammation that may involve oxidative tissue damage.
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