Cited by 312Inflammatory mediators and NSAID effectsGut microbiota and healthInflammatory Bowel Disease

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Resistance of germfree rats to indomethacin-induced intestinal lesions

Robert, André, Asano, Tomoaki·1977·Prostaglandins

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Abstract

Indomethacin given orally to conventional rats produced in three days a syndrome, often fatal, of intestinal lesions characterized by multiple ulcers and peritonitis. Male germfree rats were found to be resistant to this effect of indomethacin, while female germfree rats developed very mild lesions. Germfree rats became sensitive again to such lesions when monocontaminated with E. coli. In such animals, however, the lesions were less severe than in conventional animals, presumably because more than one microorganism is necessary for the full syndrome to develop. These results suggest that microorganisms are necessary for the development of indomethacin-induced intestinal lesions. Secondary bile acids, absent in germfree animals, may also be necessary. The prostaglandin deficiency caused by indomethacin appears to weaken the resistance of the intestinal mucosa to microorganisms and/or their toxins. The latter may then penetrate the mucosa, damage the cells and produce ulcers and perforations. Since several prostaglandins also protect against indomethacin-induced lesions, the hypothesis is advanced that certain prostaglandins may protect the mucosa ("cytoprotection") by preventing the spread of microorganisms and/or their toxin through the intestinal wall.

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Authors: Robert, A., & Asano, T.
Affiliations: University of Notre Dame (US)
Venue: Prostaglandins
Publisher: Elsevier BV
Published: 1977-08
Volume: 14
Issue: 2
Pages: 333-341
ISSN: 0090-6980 (ISSN-L)
DOI: 10.1016/0090-6980(77)90178-2
OpenAlex: W2059605635
Cited by: 312
References: 9
Citations by year: 2026: 4 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 9 · 2020: 7 · 2019: 11 · 2018: 2 · 2017: 12 · 2016: 7 · 2015: 11 · 2014: 12 · 2013: 5 · 2012: 11
FWCI: 2.60
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Prostaglandins (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
Keywords: germ-free rats, indomethacin, intestinal lesions, intestinal ulceration, peritonitis, Escherichia coli, secondary bile acids, prostaglandin deficiency, drug-induced intestinal injury, sex differences
MeSH terms: Animals, Escherichia coli, Female, Germ-Free Life, Indomethacin, Intestinal Diseases, Intestines, Male, Peritonitis, Prostaglandins E, Rats, Inbred Strains, Sex Factors, Ulcer, Rats

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Resistance of germfree rats to indomethacin-induced intestinal lesions

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