title: Protective effect of roxatidine against indomethacin-induced small intestinal mucosal injury in rats.
abstract: OBJECTIVE
  Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most significant causative factors of gastroduodenal ulcers. Recent reports have demonstrated that NSAIDs can also frequently induce ulceration and erosions of the small intestine. The aim of this study was to examine whether or not roxatidine (an H(2) receptor antagonist), which is known to increase gastric mucus in addition to inhibiting gastric acid, might suppress indomethacin-induced small intestinal mucosal injury, through an increase in mucus in rats.
  
  
  METHODS
  Rats were given two p.o. doses of roxatidine, famotidine or cimetidine before and after the s.c. indomethacin injection. The injured area of the small intestine was analyzed. To examine effects of drugs on small intestinal mucus, rats were also given two p.o. doses of roxatidine, famotidine or cimetidine, and the ratio of the periodic acid Schiff (PAS)-positive area to the area of the mucosa in the small intestine was analyzed. In addition, we evaluated the involvement of nitric oxide (NO) and prostaglandins (PG) in the effect of roxatidine on small intestinal mucus.
  
  
  RESULTS
  Roxatidine significantly ameliorated indomethacin-induced small intestinal injury and increased the PAS-stained areas in the small intestinal mucosa, while cimetidine and famotidine had no significant effect. Pretreatment with N-nitro-L-arginine methyl ester but not with indomethacin, suppressed the effect of roxatidine on small intestinal mucus, suggesting that the effect is mediated by endogenous NO but not by PG.
  
  
  CONCLUSIONS
  Roxatidine suppressed indomethacin-induced small intestinal injury in rats. One possible mechanism is an increase of small intestinal mucus, mediated by NO.
authors.affiliation: Second Department of Internal Medicine, Osaka Medical College, Takatsuki City, Osaka, Japan. in2038@poh.osaka-med.ac.jp
authors.forename: Eiji
authors.initials: E
authors.lastname: Umegaki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yoda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tokioka
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Murano
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Higuchi
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D004195:Disease Models, Animal; D015738:Famotidine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007213:Indomethacin; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009093:Mucus / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010437:Peptic Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010880:Piperidines / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011453:Prostaglandins; D009569:Nitric Oxide; D015738:Famotidine; D002927:Cimetidine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin; C053742:roxatidine acetate