In vitro and in vivo Protection against Indomethacin-Induced Small Intestinal Injury by Proton Pump Inhibitors, Acid Pump Antagonists, or Indomethacin-Phosphatidylcholine

• Published in: Digestion Vol. 86; no. 2; pp. 171 - 177
• Main Authors: Lim, Yun Jeong, Phan, Tri M., Dial, Elizabeth J., Graham, David Y., Lichtenberger, Lenard M.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2012
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacology; Animals; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Apoptosis - drug effects; Cell Survival - drug effects; Cells, Cultured; Epithelial Cells - drug effects; Gastrointestinal Hemorrhage - chemically induced; Gastrointestinal Hemorrhage - prevention & control; Indomethacin - adverse effects; Intestinal Mucosa - drug effects; Intestine, Small - drug effects; Lansoprazole; Male; Omeprazole - pharmacology; Original Paper; Phosphatidylcholines - pharmacology; Proton Pump Inhibitors - pharmacology; Pyrimidinones - pharmacology; Rats; Rats, Sprague-Dawley; Tetrahydroisoquinolines - pharmacology; Phosphatidylcholine; Indomethacin; Small intestinal injury; Acid pump antagonist; Proton pump inhibitor
• ISSN: 0012-2823; 1421-9867; 1421-9867
• DOI: 10.1159/000339882

Background/Aims: Proton pump inhibitors (PPIs) are widely used to prevent nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcers. NSAIDs produce small intestinal injury and some PPIs have been reported to protect against NSAID-induced small bowel injury in rats. The aim of this study was to compare PPIs, revaprazan, and phosphatidylcholine-associated indomethacin (Indo-PC) for protection against indomethacin (Indo)-induced small bowel injury. Methods: Rat intestinal epithelial cells (IEC-6) were pretreated with omeprazole, lansoprazole, or revaprazan prior to exposure to Indo or Indo-PC. Cell viability was assessed by methyl thiazolyl tetrazolium assay. Omeprazole, lansoprazole, or revaprazan was administered orally to rats prior to the vehicle or Indo. Indo-PC was administered alone. After 24 h, small intestinal erosions were counted; intestinal bleeding was assessed as the hemoglobin concentration of small intestinal fluid. Results: Omeprazole, lansoprazole, and revaprazan did not protect against Indo-induced IEC-6 cell injury. Indo-PC was less damaging in vitro than Indo alone. In vivo, neither omeprazole nor lansoprazole protected against Indo-induced small bowel injury; however, revaprazan pretreatment and Indo-PC resulted in significantly fewer erosions (>50% reduction) or bleeding (>80% reduction). Conclusion: PPIs showed no small bowel protective effect in vitro or in vivo. Revaprazan showed a small bowel protective effect in vivo, whereas Indo-PC was protective both in vitro and in vivo.