title: Inhibition of Helicobacter pylori-induced cyclo-oxygenase-2 aggravates NSAID-caused gastric damage in Mongolian gerbils.
abstract: BACKGROUND
  The effect of Helicobacter pylori infection on non-steroidal anti-inflammatory drug-induced gastric mucosal injury is controversial.
  
  
  OBJECTIVE
  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.
authors.affiliation: Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Futagami
authors.forename: T
authors.initials: T
authors.lastname: Hiratsuka
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: A
authors.initials: A
authors.lastname: Tatsuguchi
authors.forename: T
authors.initials: T
authors.lastname: Tsukui
authors.forename: K
authors.initials: K
authors.lastname: Miyake
authors.forename: T
authors.initials: T
authors.lastname: Akamatsu
authors.forename: M
authors.initials: M
authors.lastname: Hosone
authors.forename: C
authors.initials: C
authors.lastname: Sakamoto
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori; D007213:Indomethacin / Q000633:toxicity*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D010438:Peptic Ulcer Hemorrhage / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases; D013276:Stomach Ulcer / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D009195:Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin