Nimesulide alters cell recruitment into mitosis in murine intestinal crypts without influencing the cell production rate.
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) that exhibit COX-2 selectivity is associated with fewer gastrointestinal side effects than seen with more traditional NSAIDs. To determine whether the early effects on cell kinetics in the intestinal mucosal epithelium described after COX-2 selective inhibition are sustained following continuous therapy with these inhibitors, assessments of morphometry and cryptal cell proliferation in the murine small intestinal mucosa were made at 24 hr after treatment with indomethacin, a dual COX inhibitor (10 mg/kg body weight intraperitoneally), nimesulide, a selective COX-2 inhibitor (15 mg/kg body weight intraperitoneally), or vehicle. Nimesulide-treated intestine was elongated beyond control values, in contrast to the shorter indomethacin-treated intestine, but anomalous villous forms were present in both treated groups. Both treatments induced expansion and contraction of proliferating compartments in the crypts in different regions of the intestine but nimesulide did not alter crypt cell production rates, in contrast to the down-regulation induced by indomethacin. These findings may provide some of the fundamental basis for the gut-sparing properties seen in patients treated with COX-2 selective inhibitors.
McGarvey
M Alice
MA
Department of Anatomy, Royal College of Surgeons in Ireland, St Stephen's Green, Dublin, Ireland.
Bass
Gary
G
Ettarh
R R
RR
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D007213:Indomethacin / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D013449:Sulfonamides / Q000009:adverse effects*
D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; C012655:nimesulide; D007213:Indomethacin