| Role of bile in pathogenesis of indomethacin-induced enteropathy. | |
| | |
MedLine Citation:
|
PMID: 17151867 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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:
|
Molly Jacob; Russel Foster; Gudmundur Sigthorsson; Robert Simpson; Ingvar Bjarnason |
Related Documents
:
|
8426077 - Hyperglucagonemia and hyperdynamic circulation in rats with biliary cirrhosis. 7279787 - Morphology of liver cell tight junctions in ethinyl estradiol induced cholestasis. 1494887 - Effect of peroxisome proliferators on glutathione-dependent sulphobromophthalein excret... 6744257 - Urinary excretion of n-nitrosodimethylamine in rats after thalamonal narcosis. 2389247 - Effect of the peroxisome proliferator ciprofibrate on hepatic dna synthesis and hepatic... 10222037 - Cytochrome p450 3a degradation in isolated rat hepatocytes: 26s proteasome inhibitors a... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-12-07 |
Journal Detail:
|
Title: Archives of toxicology Volume: 81 ISSN: 0340-5761 ISO Abbreviation: Arch. Toxicol. Publication Date: 2007 Apr |
Date Detail:
|
Created Date: 2007-03-16 Completed Date: 2007-10-16 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0417615 Medline TA: Arch Toxicol Country: Germany |
Other Details:
|
Languages: eng Pagination: 291-8 Citation Subset: IM |
Affiliation:
|
Department of Biochemistry, Christian Medical College, Vellore 632002, India. jacob@cmcvellore.ac.in |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Anti-Inflammatory Agents, Non-Steroidal / toxicity* Bile / metabolism Bile Acids and Salts / pharmacology* Bile Ducts / metabolism, surgery Feces / chemistry Indomethacin / toxicity* Intestinal Absorption / drug effects Intestine, Small / drug effects*, metabolism, pathology Leukocyte L1 Antigen Complex / metabolism Male Permeability Rats Rats, Sprague-Dawley Ulcer / chemically induced*, metabolism, pathology |
| Chemical | |
Reg. No./Substance:
|
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Bile Acids and Salts; 0/Leukocyte L1 Antigen Complex; 53-86-1/Indomethacin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Direct reaction of oximes with crotylsarin, cyclosarin, or VX in vitro.
Next Document: Stent fracture in revascularization for symptomatic ostial vertebral artery stenosis.