Hydrogen sulphide protects against NSAID ‐enteropathy through modulation of bile and the microbiota
Open accessAbstract
Background and Purpose: Hydrogen sulphide is an important mediator of gastrointestinal mucosal defence. The use of non‐steroidal anti‐inflammatory drugs ( NSAIDs ) is significantly limited by their toxicity in the gastrointestinal tract. Particularly concerning is the lack of effective preventative or curative treatments for NSAID ‐induced intestinal damage and bleeding. We evaluated the ability of a hydrogen sulphide donor to protect against NSAID ‐induced enteropathy. Experimental Approach: Intestinal ulceration and bleeding were induced in Wistar rats by oral administration of naproxen. The effects of suppression of endogenous hydrogen sulphide synthesis or administration of a hydrogen sulphide donor (diallyl disulphide) on naproxen‐induced enteropathy was examined. Effects of diallyl disulphide on small intestinal inflammation and intestinal microbiota were also assessed. Bile collected after in vivo naproxen and diallyl disulphide administration was evaluated for cytotoxicity in vitro using cultured intestinal epithelial cells. Key Results: Suppression of endogenous hydrogen sulphide synthesis by β ‐cyano‐ L ‐alanine exacerbated naproxen‐induced enteropathy. Diallyl disulphide co‐administration dose‐dependently reduced the severity of naproxen‐induced small intestinal damage, inflammation and bleeding. Diallyl disulphide administration attenuated naproxen‐induced increases in the cytotoxicity of bile on cultured enterocytes, and prevented or reversed naproxen‐induced changes in the intestinal microbiota. Conclusions and Implications: Hydrogen sulphide protects against NSAID ‐enteropathy in rats, in part reducing the cytotoxicity of bile and preventing NSAID ‐induced dysbiosis.
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PPIs augmented the expression of bacteria with beta-glucuronidases activity, and this microbial imbalance could promote the spread of NSAIDs into enterohepatic circulation, increasing bile cytotoxicity and subsequently causing ulcerative lesions.
“Moreover, PPIs augmented the expression of bacteria with beta-glucuronidases activity, and this microbial imbalance could promote the spread of NSAIDs into enterohepatic circulation, increasing bile cytotoxicity and subsequently causing ulcerative lesions[99,100].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [99]
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Self-citation
- Authors
- Blackler, R. W., Motta, J., Manko, A., Workentine, M., Bercik, P., Surette, M. G., & Wallace, J. L.
- Affiliations
- McMaster University (CA)
- University of Calgary (CA)
- Department of Medicine McMaster University Hamilton ON Canada
- Corresponding author
- Wallace, John L
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2014-11-24
- Volume
- 172
- Issue
- 4
- Pages
- 992-1004
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC4314190
- OpenAlex
- W2139492524
- Cited by
- 66
- References
- 60
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 8 · 2016: 5 · 2015: 10 · 2014: 1
- FWCI
- 3.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Canadian Institutes of Health Research (FRN-12033)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- hydrogen sulfide, NSAID-induced enteropathy, naproxen, diallyl disulfide, intestinal mucosal protection, intestinal bleeding, intestinal ulceration, intestinal inflammation, gut microbiota, dysbiosis, intestinal epithelial cells, gastrointestinal toxicity
- MeSH terms
- Alanine, Allyl Compounds, Animals, Anti-Inflammatory Agents, Non-Steroidal, Bile, Cell Line, Gastrointestinal Hemorrhage, Humans, Hydrogen Sulfide, Intestinal Diseases, Intestinal Mucosa, Jejunum, Membrane Proteins, Naproxen, Sulfides, Ulcer, Rats, Wistar, Protective Agents, Cyclooxygenase 1, Microbiota
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