Hydrogen sulphide protects against NSAID-enteropathy through modulation of bile and the microbiota.

Abstract

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.

• Authors: Rory W Blackler, Jean-Paul Motta, Anna Manko, Matthew Workentine, Premysl Bercik, Michael G Surette, John L Wallace
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 172 Issue 4 Pg. 992-1004 (Feb 2015) ISSN: 1476-5381 [Electronic] England
• PMID: 25297699 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The British Pharmacological Society.

Chemical References

• Allyl Compounds
• Anti-Inflammatory Agents, Non-Steroidal
• Membrane Proteins
• Protective Agents
• Sulfides
• Naproxen
• allyl sulfide
• 3-cyanoalanine
• Cyclooxygenase 1
• Ptgs1 protein, rat
• Alanine
• Hydrogen Sulfide

Topics

• Alanine (analogs & derivatives, pharmacology)
• Allyl Compounds (therapeutic use)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal
• Bile (metabolism)
• Cell Line
• Cyclooxygenase 1
• Gastrointestinal Hemorrhage (chemically induced, drug therapy, metabolism, microbiology, pathology)
• Humans
• Hydrogen Sulfide (antagonists & inhibitors, metabolism)
• Intestinal Diseases (chemically induced, drug therapy, metabolism, microbiology, pathology)
• Intestinal Mucosa (metabolism, microbiology, pathology)
• Jejunum (metabolism, microbiology, pathology)
• Membrane Proteins (antagonists & inhibitors)
• Microbiota
• Naproxen
• Protective Agents (therapeutic use)
• Rats, Wistar
• Sulfides (therapeutic use)
• Ulcer (chemically induced, drug therapy, metabolism, microbiology, pathology)