Skip to Content
Merck
  • Hydrogen sulphide protects against NSAID-enteropathy through modulation of bile and the microbiota.

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

British journal of pharmacology (2014-10-10)
Rory W Blackler, Jean-Paul Motta, Anna Manko, Matthew Workentine, Premysl Bercik, Michael G Surette, John L Wallace
ABSTRACT

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. 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. 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. Hydrogen sulphide protects against NSAID-enteropathy in rats, in part reducing the cytotoxicity of bile and preventing NSAID-induced dysbiosis.

MATERIALS
Product Number
Brand
Product Description

Supelco
Naproxen sodium, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Naproxen sodium, meets USP testing specifications
Sigma-Aldrich
Prostaglandin E2, γ-irradiated, powder, BioXtra, suitable for cell culture
Sigma-Aldrich
Prostaglandin E2, synthetic, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Naproxen sodium, 98.0-102.0%
USP
Naproxen sodium, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Prostaglandin E2, ≥93% (HPLC), synthetic
Supelco
Dimethyl sulfoxide, for inorganic trace analysis, ≥99.99995% (metals basis)
Sigma-Aldrich
8-Octanoyloxypyrene-1,3,6-trisulfonic acid trisodium salt, suitable for fluorescence, ≥90% (HPCE)
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Naproxen, meets USP testing specifications
Supelco
Naproxen, VETRANAL®, analytical standard
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., ACS reagent, ≥99.9% (GC)
Supelco
Dimethyl sulfoxide, analytical standard
Sigma-Aldrich
Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
Sigma-Aldrich
(S)-(+)-6-Methoxy-α-methyl-2-naphthaleneacetic acid, 98%
Supelco
Naproxen, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%
USP
Dimethyl sulfoxide, United States Pharmacopeia (USP) Reference Standard
USP
Naproxen, United States Pharmacopeia (USP) Reference Standard
Naproxen, European Pharmacopoeia (EP) Reference Standard
Dinoprostone, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., dried, ≤0.02% water
Dimethyl sulfoxide, European Pharmacopoeia (EP) Reference Standard