title: Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine.
abstract: Proton pump inhibitors (PPIs) have been shown to be effective in preventing gastric and duodenal ulcers in high-risk patients taking nonsteroidal anti-inflammatory drugs (NSAIDs); by contrast, scarce information is available concerning the effects of PPIs on intestinal damage induced by NSAIDs in humans or in experimental animals. We examined the effects of lansoprazole and omeprazole on the intestinal injury induced by indomethacin in the conscious rat. PPIs were administered by the intragastric route at 30, 60 and 90 micromol/kg, 12 h and 30 min before and 6 h after indomethacin treatment. The effects of omeprazole and lansoprazole were evaluated on: (1) macroscopic and histologic damage; (2) mucosal polymorphonuclear cell infiltration; (3) oxidative tissue damage and (4) bacterial translocation from lumen into the intestinal mucosa. Lansoprazole and omeprazole (at 90 micromol/kg) significantly decreased (P<0.01) the macroscopic and histologic damage induced by indomethacin in the rat small intestine. Furthermore, both drugs greatly reduced (P<0.01) the associated increases in myeloperoxidase levels and lipid peroxidation induced by indomethacin, whereas they only moderately affected (P<0.05) the translocation of enterobacteria from lumen into the intestinal mucosa. These data demonstrate that omeprazole and lansoprazole can protect the small intestine from the damage induced by indomethacin in the conscious rat. The intestinal protection, possibly related to antioxidant and anti-inflammatory properties of these drugs, may suggest new therapeutic uses of PPIs in intestinal inflammatory diseases.
authors.affiliation: Department of Human Anatomy, Pharmacology and Forensic Medicine, University of Parma, Via Volturno 39, Parma, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Pozzoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Menozzi
authors.forename: Daniela
authors.initials: D
authors.lastname: Grandi
authors.forename: Elvira
authors.initials: E
authors.lastname: Solenghi
authors.forename: Maria C
authors.initials: MC
authors.lastname: Ossiprandi
authors.forename: Chiara
authors.initials: C
authors.lastname: Zullian
authors.forename: Simone
authors.initials: S
authors.lastname: Bertini
authors.forename: Giulia M
authors.initials: GM
authors.lastname: Cavestro
authors.forename: Gabriella
authors.initials: G
authors.lastname: Coruzzi
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001420:Bacteria, Aerobic / Q000187:drug effects; D001421:Bacteria, Anaerobic / Q000187:drug effects; D018988:Bacterial Translocation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology; D007441:Intubation, Gastrointestinal; D007583:Jejunum / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D064747:Lansoprazole; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009853:Omeprazole / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D054328:Proton Pump Inhibitors; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D008315:Malondialdehyde; D009195:Peroxidase; D009853:Omeprazole; D007213:Indomethacin