Indomethacin inhibits cell proliferation in the oxyntic epithelium of the rat

The aim of this investigation was to examine the action of parenteral indomethacin and oral prostaglandin E2 on cell proliferation in the rat oxyntic mucosa. Groups of Sprague Dawley rats were treated with either 1.5 mg/kg indomethacin subcutaneously, 5 mg/kg oral prostaglandin E2 or placebo, twice daily during 5 days. All rats were killed exactly 4 hours after mitotic arrest with vincristine, and a biopsy specimen from the oxyntic mucosa was processed for routine microscopic evaluation. Mitotic figures were distributed cluster-like along the oxyntic mucosa alternating with mitosis-free areas. The total number of mitotic figures in 8 mm of mucosa was significantly reduced by administration of indomethacin (p < 0.05). In rats given indomethacin, 32.5% of the examined mucosa did not have mitotic figures, which is significantly higher than 14.3% as observed in placebo-treated rats (p < 0.05). Both rats treated with indomethacin and with prostaglandin E2 had fewer microscopic fields containing 5-6 mitotic figures than placebo-treated animals (p < 0.05). The maximal length of mitosis-free areas was 0.6 (0.6-0.9) mm in rats given indomethacin which is significantly larger than 0.4 (0.2-0.4) mm observed in controls (p < 0.05). Indomethacin produced epithelial atrophy as shown by a significant reduction of the epithelial height observed in those rats compared to controls (p < 0.05). The inhibition of cell proliferation observed in the oxyntic mucosa of rats treated with the cyclooxygenase blocker indicates that an important physiological role of endogenous prostaglandin is to maintain the proliferative activity of the epithelium at a high level.