title: Role of bile in pathogenesis of indomethacin-induced enteropathy.
abstract: Ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) causes an enteropathy. The pathogenesis involves biochemical initiation of intestinal mucosal damage due to NSAID-induced inhibition of cyclooxygenase and the topical effects of these drugs. These effects lead to increased intestinal permeability and inflammation. Luminal bile acids play a controversial role in the damage produced by these drugs. The aim of this study was to determine the role of bile in producing the enteropathy caused by indomethacin, an NSAID commonly used in toxicity studies. Sprague-Dawley rats were subjected to bile duct ligation. Twenty-four hours later, they were dosed with indomethacin. Intestinal permeability ((51)Cr-EDTA) and inflammation (faecal calprotectin) were measured in the animals at various time periods after the dose. Intestinal permeability was significantly higher in rats 1-6 h after dosing with indomethacin, but not at 24-29 h or day 4, when compared with corresponding values for control animals. Excretion of faecal calprotectin was elevated in the indomethacin-treated rats. The drug-treated animals showed no evidence of ulceration when they were sacrificed 29 h or a week after the dose of indomethacin. Bile acids per se did not affect intestinal permeability or faecal excretion of calprotectin, when given along with indomethacin or its vehicle. We conclude that macroscopic small bowel damage does not occur with indomethacin if bile is excluded, despite the induction of permeability and inflammation. This study highlights the importance of luminal factors, such as bile, in producing indomethacin-induced ulceration in the rat small intestine.
authors.affiliation: Department of Biochemistry, Christian Medical College, Vellore 632002, India. jacob@cmcvellore.ac.in
authors.forename: Molly
authors.initials: M
authors.lastname: Jacob
authors.forename: Russel
authors.initials: R
authors.lastname: Foster
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Sigthorsson
authors.forename: Robert
authors.initials: R
authors.lastname: Simpson
authors.forename: Ingvar
authors.initials: I
authors.lastname: Bjarnason
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001652:Bile Ducts / Q000378:metabolism / Q000601:surgery; D005243:Feces / Q000737:chemistry; D007213:Indomethacin / Q000633:toxicity*; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008297:Male; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D014456:Ulcer / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001647:Bile Acids and Salts; D039841:Leukocyte L1 Antigen Complex; D007213:Indomethacin