Indomethacin-induced gastric antral damage in hamsters: are neutrophils involved?
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.
Fitzpatrick
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Gastrointestinal Inflammation Department, Maryland Research Laboratories, Otsuka America Pharmaceutical Inc., Rockville, Maryland 20850, USA.
Sakurai
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D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D006224:Cricetinae; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity*; D008297:Male; D008647:Mesocricetus; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011706:Pyloric Antrum; D015363:Quinolones / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015363:Quinolones; D009195:Peroxidase; C052785:rebamipide; D000409:Alanine; D007213:Indomethacin; D008727:Methotrexate