Aggravating Process Induced by Indomethacin on Chronic Gastric Lesion in Rat. Role of Polymorphonuclear Leucocytes

Abstract

The present study examines the indomethacin-provoked aggravation of chronic ulceration induced by acetic acid in rats. The drug was administered in a single dose, 7 and 14 days after provocation of ulceration. The changes induced by indomethacin in other groups of animals that had been treated for 7 and 14 days with hydroxyurea (which provokes a marked leucopenia) were also studied. The results obtained demonstrate that indomethacin does not significantly modify the macroscopic index of ulceration nor vascular permeability in the majority of the groups tested. Only in the group that received hydroxyurea for 14 days was there an increase in both parameters. Myeloperoxidase activity was assayed and used as an index of leucocyte infiltration in an attempt to relate the increase in this activity with a gastrolesive effect. Application of acetic acid produced a significant increase in this activity 7 days after induction of chronic injury. Administration of hydroxyurea intraperitoneally was associated with a decrease in the severity of chronic ulceration and neutrophil infiltration into the gastric mucosa. This effect was detectable enzymatically and microscopically. The groups that received indomethacin showed an increase in myeloperoxidase activity, although this increase was only significant in the animals treated with hydroxyurea for 7 and 14 days. The results suggest that the aggravation provoked by indomethacin is greater when the ulcer curing process is more advanced.

Contribution of NO synthases to neutrophil infiltration in the gastric mucosal lesions in rats with water immersion restraint stress

“…In this study, we examined whether or not changes in gastric mucosal cNOS and iNOS activities contribute to neutrophil infiltration into the gastric mucosa of rats with WIR stress. The neutrophil infiltration into the gastric mucosal tissues was checked by MPO activity, because MPO assay has been widespreadly used as an index of neutrophil infiltration in various experimental gastric injuries [24–31], colitis [32], and human gastric ulcer [33]. The development of gastric mucosal lesions was found to occur with an increase in gastric mucosal MPO activity in rats subjected to WIR stress over a 6 h period.…”

Antiinflamatory Agents Less Dangerous for Gastrointestinal Tract

“…Oxygen-derived free radicals may contribute to the formation and development of chronic lesions and they are generated from neutrophils, but not from the xanthine oxidase pathway. These inflammatory cells may, therefore, have a lesive role in the origin and course of acetic acid ulcer disease [73]. Neutrophils play an important role in the gastric mucosal dysfunction associated with ischemiareperfusion.…”