title: NSAID-induced small intestinal damage--roles of various pathogenic factors.
abstract: OBJECTIVE
  NSAID-induced enteropathy has been the focus of recent basic and clinical research subsequent to the development of the capsule endoscope and double-balloon endoscope. We review the possible pathogenic mechanisms underlying NSAID-induced enteropathy and discuss the role of the inhibition of COX-1/COX-2 and the influences of food as well as various prophylactic treatments on these lesions.
  
  
  METHODS
  Studies were performed in experimental animals.
  
  
  RESULTS
  Multiple factors, such as intestinal hypermotility, decreased mucus secretion, enterobacteria, and upregulation of iNOS/NO expression, are involved in the pathogenesis of NSAID-induced enteropathy, in addition to the decreased production of PGs due to the inhibition of COX. Enterobacterial invasion is the most important pathogenic event, and intestinal hypermotility, which was associated with this event, is essential for the development of these lesions. NSAIDs also upregulate the expression of COX-2, and the inhibition of both COX-1 and COX-2 is required for the intestinal ulcerogenic properties of NSAIDs to manifest. NSAID-induced enteropathy is prevented by PGE2, atropine, ampicillin, and aminoguanidine as well as soluble dietary fiber, and exacerbated by antisecretory drugs such as proton pump inhibitors.
  
  
  CONCLUSIONS
  These findings on the pathogenesis of NSAID-induced enteropathy will be useful for the future development of intestinal-sparing alternatives to standard NSAIDs.
authors: Department of Pharmacology and Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Misasagi, Yamashina, Japan.
authors: Koji
authors: K
authors: Takeuchi
authors: Hiroshi
authors: H
authors: Satoh
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D004043:Dietary Fiber / Q000009:adverse effects / Q000627:therapeutic use; D015232:Dinoprostone / Q000627:therapeutic use; D004755:Enterobacteriaceae; D018565:Food-Drug Interactions; D005769:Gastrointestinal Motility / Q000187:drug effects; D007410:Intestinal Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D065129:Pre-Exposure Prophylaxis / Q000379:methods; D011453:Prostaglandins / Q000096:biosynthesis; D054328:Proton Pump Inhibitors / Q000009:adverse effects; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004043:Dietary Fiber; D011453:Prostaglandins; D054328:Proton Pump Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D015232:Dinoprostone