Polyamines and ornithine decarboxylase during repair of duodenal mucosa after stress in rats.

This investigation shows whether polyamines and ornithine decarboxylase have a role in duodenal mucosal repair following stress-induced microscopic damage. Rats were fasted for 22 hours, placed in restraint cages, and immersed in water to the xiphoid process for 6 hours. Animals were killed either immediately after the period of stress or at 2-hour intervals up to 24 hours thereafter. Duodenal mucosa was examined histologically, and ornithine decarboxylase and polyamine levels were measured. Ornithine decarboxylase activity was increased significantly up to 6 hours following stress, peaking at 4 hours at a level 10 times the prestress control. By 8 hours, enzyme activity had returned to near normal. Increases in mucosal putrescine, spermidine, and spermine content paralleled the changes in ornithine decarboxylase activity and peaked 4 hours after stress. Stress resulted in microscopic damage evidenced by a nearly complete absence of villi. Significant macroscopic lesions were not present following stress. Mucosal repair was evident 12 hours after stress and almost complete by 24 hours, although the restituted villi were short and blunted. The decreases in mucosal DNA, RNA, and protein content caused by stress were restored and reached near-normal levels 12 hours after the period of stress. In animals given the specific inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine, increases in duodenal mucosal ornithine decarboxylase activity and polyamine levels were inhibited and mucosal repair was almost completely prevented following stress. alpha-Difluoromethylornithine also prevented the recovery of DNA, RNA, and protein content of the duodenal mucosa. These results indicate that duodenal mucosal damage following stress is repaired rapidly; the repair process is accompanied by significant increases in ornithine decarboxylase activity and polyamine levels; and the increases in ornithine decarboxylase and polyamines are absolutely required for the normal repair of the mucosa.