Here we conducted experiments to elucidate whether PPIs in comparison to an acid pump antagonist could protect against NSAID-induced intestinal injury. intestinal erosions were counted; intestinal bleeding was assessed as 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 only. In vivo neither omeprazole nor lansoprazole safeguarded against Indo-induced small bowel injury, however, revaprazan pretreatment and Indo-PC resulted in significantly fewer erosions ( 50% reduction) or bleeding ( 80% reduction). Summary 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 protecting both in vitro and in vivo. Intro Nonsteroidal anti-inflammatory medicines (NSAIDs) are extensively used for his or her analgesic, antipyretic and anti-inflammatory properties. However, NSAIDs can induce gastrointestinal (GI) injury which is an important issue in medical practice. Proton pump inhibitors (PPI) are widely used to reduce NSAID-induced peptic ulcer and are currently recommended for the prevention of NSAID-induced peptic ulcer in high risk organizations. NSAID induced small intestinal injury has been reported in 60C70% of users [2C5]. Although NSAID-induced small intestinal injury is typically asymptomatic, it can result in clinical outcomes such as overt bleeding, stricture or small bowel perforation. The pathophysiologic mechanism for small intestinal injury (22R)-Budesonide induced by NSAIDs has not been fully elucidated, nor have reliably protecting medicines been recognized. Recently, studies in rats have shown that some PPIs have a protective part against NSAID-induced small intestinal injury acting through anti-inflammatory and antioxidant mechanisms, and not from the suppression of acid secretion[6C8]. However, in other studies, PPIs have been reported to exacerbate NSAID-induced lower gut injury . This paper wanted to test and compare the effects of an acidity pump (22R)-Budesonide antagonist (APA), revaprazan  and administration of the NSAID indomethacin linked to phosphatidylcholine (Personal computer) (i.e., the PC-associated NSAIDs indomethacin, Indo-PC]. Safety against indomethacin (Indo)-induced small intestinal injury was evaluated using both and systems. Methods Materials Omeprazole was purchased from LKT laboratories Inc. (St. Paul, MN), and lansoprazole and Indo from Sigma Aldrich (St. Louis, MO). Revaprazan was a gift from Yuhan Corp. (Seoul, South Korea). (22R)-Budesonide Indo-PC was prepared according to published protocols  and was a 1:2 preparation (by excess weight) of Indo and Phospholipon 90G (Lipoid Corp., Germany). system To assess whether there was direct protective effect of medicines system Approval for those protocols was from the institutional Animal Welfare Committee which follows the guidelines and is accredited by the US Public Health Services. Male Sprague-Dawley rats (Harlan Sprague-Dawley, Indianapolis, IN, USA) were used in all studies. Animals were managed on a 12 hours light/dark cycle with food and water provided system The cell viability was dose-dependently reduced by increasing concentrations of Indo (Number 1A). The concentration of Indo that reduced cell (22R)-Budesonide viability 50% compared to the untreated control was 1 mM and it was used in further studies. The concentrations of drug that did not affect viability were 0.1 mM concentration of omeprazole, 0.05 mM of lansoprazole or 0.0025mM of revaprazan (data not shown). MTT assays showed that omeprazole, lansoprazole and revaprazan failed to protect against 1 mM Indo-induced intestinal cell injury (Number 1B). In contrast, Indo-PC at 1 mM was significantly less damaging (approximately 35%) than Indo alone (Number 2A). Using caspase-3/7 activity like a marker of apoptosis also showed that Indo-induced apoptosis was significantly less with Indo-PC compared to Indo only (Number 2B). Open in a separate window Number 1 studies – Indo. (A) MTT assay showed that indomethacin decreased cell viability inside a dose-dependent manner. (B) MTT assay showed that omeprazole, lansoprazole and revaprazan did not reverse the Indomethacin-induced reduction in intestinal cell viability. Open in a separate window Number 2 studies C Indo-PC. (A) MTT assay showed Indo-PC at 1mM was less injurious than Indo only. (B) Caspase-3/7 assay showed IFITM1 that Indo-PC induced less apoptosis than Indo only. *=p 0.001 versus Control; #=p 0.001 versus Indo. system Gross small intestinal lesion scores When given (22R)-Budesonide to rats, Indo at 10 mg/kg caused small intestinal injury consisting of punctuate hemorrhagic places or erosions on the small intestinal mucosa (Number 3A). There was no concomitant belly.