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Indomethacin-induced gastric antral damage in hamsters: are neutrophils involved?
L R Fitzpatrick1, K Sakurai, T Le
1Gastrointestinal Inflammation Department, Maryland Research Laboratories, Otsuka America Pharmaceutical Inc., Rockville, Maryland 20850, USA.
Background:
A direct role for neutrophils in the pathophysiology of indomethacin-induced gastric damage is controversial. Therefore, such damage was evaluated in hamsters.
Methods:
Gastric antral damage was evaluated 4 h after the oro-gastric administration of indomethacin (30 mg/kg). Prior to indomethacin, hamsters were treated with various pharmacological agents: rebamipide, methotrexate or anti-neutrophil serum (ANS). The number of circulating neutrophils was determined from Wright-Giemsa stained blood smears. Myeloperoxidase (MPO) activity was measured as a marker of gastric antral neutrophil infiltration.
Results:
Indomethacin caused primarily gastric antral damage. By histology, this damage did not penetrate the muscularis mucosa. A significant increase in gastric antral MPO activity was also found in indomethacin-treated hamsters. Rebamipide decreased macroscopic gastric antral damage in a dose-related fashion. Methotrexate treatment reduced the circulating blood neutrophil number by 38-44%, but did not affect gastric damage. ANS treatment resulted in near complete neutropenia, and also in a substantial reduction (84%) in gastric antral MPO activity. However, gastric antral damage was not significantly altered by ANS.
Conclusions:
Neutrophils are not directly involved in the pathophysiology of indomethacin-induced damage to the hamster gastric antrum.