STRUCTURAL AND MORPHOMETRIC ANALYSIS OF MURINE SMALL-INTESTINE AFTER INDOMETHACIN ADMINISTRATION

Indomethacin, a nonsteroidal anti-inflammatory drug, induces the formation of gastrointestinal ulceration both in experimental animals and in humans. A study of indomethacin-induced ulcers in the mouse showed that two doses of indomethacin, each administered subcutaneously at 85 mg/kg body weight, induced well-defined gastrointestinal ulcers in C57 mice, accompanied by inflammatory and vascular changes in the stomach and small intestine. Maximal damage was observed 20 h after the second dose of indomethacin. Morphometric analysis identified changes in all compartments of the small intestine. There was a marked reduction in the length of the small intestine, intestinal dilatation, a significant decrease in villous height, with the formation of subepithelial blisters or blebs within villi, and submucosal vascular dilatation. There was no change in the number of villi or of submucosal arterioles or in the total amount of muscle present in the wall of the intestine. The tissue changes identified in this study may have implications for gut function at specific periods during indomethacin treatment.