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Cited by 271Inflammatory mediators and NSAID effectsSulfur Compounds in BiologyHydrogen's biological and therapeutic effects

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

Gastrointestinal safety and anti-inflammatory effects of a hydrogen sulfide-releasing diclofenac derivative in the rat

Wallace, John L., Caliendo, Giuseppe, Santagada, Vincenzo, Cirino, Giuseppe, Fiorucci, Stefano·2007·Gastroenterology
DOI 10.1053/j.gastro.2006.11.042
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Abstract

Background & aims Gastrointestinal damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) remains a significant clinical problem. Hydrogen makes an important contribution to mucosal defense, and NSAIDs can suppress its synthesis. In this study, we evaluated the gastrointestinal safety and anti-inflammatory effects of a novel "HS-NSAID" (ATB-337) that consists of diclofenac linked to a hydrogen sulfide-releasing moiety.Methods The gastrointestinal injury-inducing effects of single or repeated administration of diclofenac versus ATB-337 were compared in rats, as were their effects on prostaglandin synthesis and cyclooxygenase-1 and -2 activities. The ability of these drugs to reduce carrageenan-induced paw edema and to elicit leukocyte adherence to the vascular endothelium (intravital microscopy) were also examined in rats.Results Diclofenac (10-50 micromol/kg) dose-dependently damaged the stomach, while ATB-337 did not. Repeated administration of diclofenac caused extensive small intestinal damage and reduced hematocrit by 50%. ATB-337 induced >90% less intestinal damage and had no effect on hematocrit. Diclofenac, but not ATB-337, elevated gastric granulocyte infiltration and expression of tumor necrosis factor alpha, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1. ATB-337 inhibited cycloxygenase-1 and cyclooxygenase-2 activity as effectively as diclofenac. ATB-337 did not induce leukocyte adherence, whereas diclofenac did, and was more potent at reducing paw edema.Conclusions An HS-NSAID spares the gastric mucosa of injury despite markedly suppressing prostaglandin synthesis. This effect may be related to hydrogen sulfide-mediated inhibition of tumor necrosis factor-alpha expression and of the leukocyte adherence to vascular endothelium normally induced by cyclooxygenase inhibitors.

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Research works printed but not linked: 1

  1. Fiorucci, 2006, Enhanced anti-inflammatory activity of hydrogen sulfide releasing derivative of mesalamine in rodent models of colitis involves direct inhibition of Nf-KB (abstr), Gastroenterology, 130, A348

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Metadata

Authors
Wallace, J. L., Caliendo, G., Santagada, V., Cirino, G., & Fiorucci, S.
Affiliations
  • University of Calgary (CA)
  • University of Naples Federico II (IT)
Corresponding author
Wallace, John L.
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2007-01
Volume
132
Issue
1
Pages
261-271
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2006.11.042
OpenAlex
W2163895651
Cited by
271
References
39
Citations by year
2026: 6 · 2025: 3 · 2024: 6 · 2023: 9 · 2022: 13 · 2021: 13 · 2020: 12 · 2019: 13 · 2018: 9 · 2017: 23 · 2016: 19 · 2015: 26 · 2014: 23 · 2013: 22 · 2012: 18
FWCI
6.89
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Hydrogen's biological and therapeutic effects
Keywords
diclofenac, NSAID-induced gastrointestinal injury, gastroprotection, cyclooxygenase-1, cyclooxygenase-2, prostaglandin synthesis, TNF-α, leukocyte adhesion, paw edema, small bowel injury, hematocrit, anti-inflammatory activity
MeSH terms
Animals, Anti-Inflammatory Agents, Non-Steroidal, Blood Platelets, Diclofenac, Gastric Acid, Heterocyclic Compounds, 1-Ring, Humans, Hydrogen Sulfide, Male, Platelet Aggregation Inhibitors, Stomach, Drug Design, Cyclooxygenase Inhibitors, Rats, Wistar, Rats, Cyclooxygenase 1, Cyclooxygenase 2

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