Role of lymphoid nodules in pathogenesis of indomethacin-induced gastric lesions in dogs.

Pathogenesis of indomethacin-induced gastric lesions in beagles was studied morphologically. While a single oral administration of indomethacin (20 mg/kg) did not induce visible lesions in the stomach of male beagles, repeated administration once daily for 5 or 10 days induced gastric erosions or ulcers, mainly in the antrum. When this compound was given once or repeatedly, histological examination showed that the total number of lymphoid nodules both in the fundus and antrum tended to increase or significantly increased. The number of large nodules (over 350 micron in diameter) was significantly increased, particularly in the antrum. Some of these enlarged nodules seen at the surface of the mucosa showed damage at the luminal area, and the lesions were microscopically visible. Indomethacin is known to disrupt the gastric mucosal barrier in dogs, leading to increased back-diffusion of acid. Our findings and those of others suggest that indomethacin may induce lesions in specific portions of the dog stomach, initiated by enlargement of lymphoid nodules followed by damage to some of these nodules, probably due to a corrosive effect of gastric juice through the disrupted mucosal barrier.