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Inhibition of Helicobacter pylori ‐induced cyclo‐oxygenase‐2 aggravates NSAID‐caused gastric damage in Mongolian gerbils
Author(s) -
Futagami S.,
Hiratsuka T.,
Wada K.,
Tatsuguchi A.,
Tsukui T.,
Miyake K.,
Akamatsu T.,
Hosone M.,
Sakamoto C.,
Kobayashi M.
Publication year - 2002
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.2002.01211.x
Subject(s) - helicobacter pylori , medicine , indometacin , gastric mucosa , stomach , pharmacology , gastritis , immunology , enzyme inhibitor , chemistry , enzyme , biochemistry , prostaglandin endoperoxide synthase
Background: The effect of Helicobacter pylori infection on non‐steroidal anti‐inflammatory drug‐induced gastric mucosal injury is controversial. Aim: To examine the effect of the interaction between H. pylori and non‐steroidal anti‐inflammatory drugs on gastric mucosal injury. Methods: Mongolian gerbils infected with H. pylori were treated with indometacin at 8 mg/kg for 2 days or 7 days. Mucosal damage was assessed by macroscopic and histological examination, and myeloperoxidase activity was measured as an index of neutrophil infiltration. The expression levels of cyclo‐oxygenase proteins were determined by Western blot analysis and cyclo‐oxygenase activity. Results: A 2‐day course of indometacin did not cause an increase in gastric damage in H. pylori ‐infected Mongolian gerbils compared to uninfected gerbils, while a 7‐day course of indometacin caused additive gastric damage in H. pylori ‐infected animals. H. pylori infection induced cyclo‐oxygenase‐2 expression in the stomach. Treatment with indometacin for 2 days did not significantly affect cyclo‐oxygenase activity in H. pylori ‐infected animals, while treatment for 7 days inhibited both cyclo‐oxygenase‐1 and cyclo‐oxygenase‐2 activities. Pre‐treatment with a selective cyclo‐oxygenase‐2 inhibitor aggravated mucosal injury in H. pylori ‐infected animals treated or not treated with indometacin for 2 days. Conclusions: Our results suggest that cyclo‐oxygenase‐2 protein induced by H. pylori infection may be involved in the defence of the gastric mucosa against damage caused by non‐steroidal anti‐inflammatory drugs. Therefore, inhibition of cyclo‐oxygenase‐2 activity may enhance non‐steroidal anti‐inflammatory drug‐caused gastric damage in H. pylori ‐infected animals.