Role of ornithine decarboxylase in repair of gastric mucosal stress ulcers.

The purpose of this study was to determine whether ornithine decarboxylase (ODC) has a role in mucosal repair during the first 24 h after stress-induced damage. Rats were fasted 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for 6 h. Animals were killed either immediately after the period of stress or at 2-h intervals up to 24 h thereafter. Gastric mucosal ODC increased significantly from 0 to 12 h and peaked 4 h after the 6-h stress period. By 24 h enzyme activity in the gastric mucosa was near normal. Macroscopic lesions were regularly produced after 6 h of stress. Histologically, stress caused extensive damage to the superficial epithelial cells, extending in some cases into the mucosa and beyond the basal lamina. However, after stress the mucosa recovered quickly, returning to near normal 24 h later. The decreases in mucosal content of DNA, RNA, and protein caused by stress also were restored and reached near-normal levels 24 h after stress. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, not only inhibited the ODC activity but significantly delayed the recovery from injury as well. DFMO also prevented the restoration of DNA, RNA, and protein content of the gastric mucosa. In conclusion, stress-induced gastric mucosal lesions are accompanied by significant increases in ODC activity. The increased ODC is necessary for the normal repair of the mucosa.