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Permissive role of neutrophils in pathogenesis of indomethacin-induced gastric lesions in rats

Keizo Suzuki, Hideo Araki, Yusaku Komoike, Koji Takeuchi

Med Sci Monit 2000; 6(5): CR908-914

ID: 507946

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Background:     We examined the possible role of neutrophils in the pathogenesis of indomethacin-induced gastric lesions, in comparison with prostaglandin (PG) deficiency.
Material/Methods:     Rats were given indomethacin (35 mg/kg, s.c.) and killed 4 hr later. Gastric motility, mucosal PGE2 levels, and myeloperoxidase (MPO) activity were measured following indomethacin. Atropine was given s.c. 30 min before administration of indomethacin, while 16, 16-dimethyl PGE2 (dmPGE2) or anti-rat neutrophil antiserum (ANS) was given i.v. 10 min or 1 hr, respectively, before indomethacin treatment.
Results:     Indomethacin reduced PGE2 contents in the stomach and produced hemorrhagic lesions in the stomach, with an increase of gastric motility and MPO activity. Indomethacin-induced gastric lesions were significantly prevented by dmPGE2 as well as atropine, at any time points during a 4 hr-test period. By contrast, the pretreatment of ANS did not prevent the development of gastric lesions when examined at either 1, 2 or 3 hr following indomethacin, but significantly reduced the severity of these lesions at 4 hr after indomethacin treatment. Both dmPGE2 and atropine inhibited the increase of gastric motility and MPO activity in response to indomethacin, whereas ANS prevented the increase of MPO activity, without any effect on the gastric hypermotility.
Conclusions:     These results confirmed that indomethacin-induced gastric lesions occurred in association with gastric hypermotility, in both atropine and PG-sensitive manners, and further suggest that the neutrophil activation/migration is not sufficient by itself to induce damage in the stomach and may be implicated in the process of later extension of damage.

Keywords: Rat, gastric motility, anti-neutrophil serum prostaglandin E2, neutrophil, Indomethacin