title: Suppression of contractile activity in the small intestine by indomethacin and omeprazole.
abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat a number of conditions, and proton pump inhibitors (PPIs) are often used to prevent NSAID-induced gastric mucosal damage; however, the effects of NSAIDs on intestinal motility are poorly understood. The purpose of the present study is to determine the effects of a prototypical NSAID, indomethacin, either alone or in conjunction with the PPI omeprazole, on intestinal motility. Rats were randomly divided into four groups treated with vehicle, omeprazole, indomethacin, or a combination of indomethacin and omeprazole. Intestinal motility and transit were measured along with inflammatory mediators in the intestinal smooth muscle, markers of mucosal damage, and bacterial counts in the intestinal wall. Indomethacin, but not omeprazole, caused mucosal injury indicated by lower gut bleeding; however, both omeprazole and indomethacin suppressed contractile activity and frequency in the distal part of the small intestine. Cotreatment with omeprazole did not reduce indomethacin-induced intestinal bleeding. Furthermore, although indomethacin caused increased inflammation as indicated by increased edema development and inflammatory mediators, cotreatment with omeprazole did not reduce inflammation in the intestinal smooth muscle or prevent the increased bacterial count in the intestinal wall induced by indomethacin. We conclude that both NSAID and PPI treatment suppressed contractile activity in the distal regions of the small intestine. The suppression of intestinal contractility was associated with increased inflammation in both cases; however, indomethacin and omeprazole appear to affect intestinal motility by different mechanisms.
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Houston, Texas.
authors.forename: Lenard M
authors.initials: LM
authors.lastname: Lichtenberger
authors.affiliation: Department of Pediatric Surgery, University of Texas Medical School at Houston, Houston, Texas; and.
authors.forename: Deepa
authors.initials: D
authors.lastname: Bhattarai
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Houston, Texas.
authors.forename: Tri M
authors.initials: TM
authors.lastname: Phan
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Medical School at Houston, Houston, Texas.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Dial
authors.affiliation: Department of Pediatric Surgery, University of Texas Medical School at Houston, Houston, Texas; and karen.l.davis@uth.tmc.edu.
authors.forename: Karen
authors.initials: K
authors.lastname: Uray
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D004751:Enteritis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D007213:Indomethacin / Q000633:toxicity*; D018836:Inflammation Mediators / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009853:Omeprazole / Q000633:toxicity*; D054328:Proton Pump Inhibitors / Q000633:toxicity*; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D018836:Inflammation Mediators; D054328:Proton Pump Inhibitors; D009853:Omeprazole; D007213:Indomethacin
keywords: indomethacin; inflammation; intestinal motility; omeprazole