Nimesulide Inhibits Crypt Epithelial Cell Proliferation at 6 Hours in the Small Intestine in CD-1 Mice

To determine whether the gut-sparing selectivity of cyclooxygenase-2 inhibitors is related to early crypt kinetic mechanisms, this study compared the primary effects on small intestinal mucosal epithelial cell proliferation and morphometry of a nonselective dual cyclooxygenase inhibitor, indomethacin, with a cyclooxygenase-2 selective inhibitor, nimesulide. Indomethacin downregulated the crypt cell production rate in the proximal small intestine, and nimesulide reduced cell proliferation in the proximal and distal small intestine. Compared to controls, there were smaller proliferating compartments in the crypts in midintestinal segments in both indomethacin- and nimesulide-treated groups, but more dividing cells in the distal intestine in indomethacin-treated group. Crypt cellularity, numbers, and width were unchanged from control values in both treated groups, suggesting a reduction in crypt cell emigration. Despite its selectivity for inhibiting cyclooxygenase-2, nimesulide induces similar but widespread initial effects on intestinal cell kinetics when compared to indomethacin.