INDOMETHACIN INHIBITS CELL-PROLIFERATION AND INCREASES CELL LOSSES INRAT GASTROINTESTINAL EPITHELIUM

Gastrointestinal cell proliferation was estimated in histological sect ions of rats treated with low and high doses of parenteral indomethaci n for 3 to 60 days. Mitoses were arrested with vincristine and cells i n S phase were labeled with tritiated thymidine. Short-term, low-dose treatments reduced the mitotic activity in the oxyntic and small intes tinal epithelium, whereas moderate doses restored the mitotic index an d high doses increased the proliferative activity and produced epithel ial hyperplasia. Long-term, low-dose treatments increased cell prolife ration in the small intestine and reduced the number of villous cells. Indomethacin did not affect the proliferative response elicited by re feeding in the oxyntic mucosa, but the simultaneous administration of prostaglandin E(2) analog increased the number of arrested mitoses. Th e turnover of labeled cells was accelerated by indomethacin, particula rly in the small intestine. These findings indicate that prostaglandin s are regulators of the cell kinetics of the gastrointestinal epitheli um but, at the same time, they disclose the presence of trophic mechan isms that are independent of the synthesis of endogenous prostaglandin s.