Showing papers in "Ulcer research in 2008"

Therapeutic effect of shi-219, a novel water soluble prodrug of eg626 (phtalazinol), on mouse dextran sodium sulfate-induced colitis

Abstract: Cytokines such as IL-1β, tumor necrosis factor (TNF)-α, IL-6 and IL-8 are increased, and leukotriene (LT)B4, thromboxane (TX)B2 and PGE2 participate in inflamed colonic mucosa after administration of mouse dextran sodium sulfate (DSS). EG626 (Phthalazinol), has been shown to inhibit cyclic AMP phosphodiesterase in arteries and platelets, has an effect of anti-inflammation. The effect of SHI-219, a novel water soluble prodrug of EG626, was examined in mouse DSS-induced colitis using drinking water containing 5% DSS. When SHI-219 was given everyday, the disease activity index (DAI) representing clinical symptoms improved and the histological score decreased; furthermore, IL-1β, IL-6, and TNF-α concentrations in rectal mucosa were lower compared with the Control group. Also TXB2 and LTB4 concentrations in rectal mucosa were lower, but PGE2 concentrations in rectal mucosa were not inhibited. And then Cyclooxygenase (COX)-2 expression also correlated with the degree of inflammation in the intestinal mucosa in the SHI-219 -treated group, indicating that SHI-219 did not inhibit COX-2 expression by immunohistochemical staining. These results suggest that administration of SHI-219 may be effective in ulcerative colitis.