Format

Send to

Choose Destination
  • Showing results for the novel compound sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease. Your search for The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary diseas retrieved no results.
Sci Rep. 2016 May 27;6:26928. doi: 10.1038/srep26928.

The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease.

Author information

1
University of Groningen, Department of Molecular Pharmacology, Groningen, the Netherlands.
2
GRIAC research institute, University of Groningen, University Medical Center Groningen, the Netherlands.
3
Sulfateq B.V. Groningen, the Netherlands.
4
University of Groningen, University Medical Center Groningen, Dept. Pathology and Medical Biology, Laboratory for Cardiovascular Regenerative Medicine, Groningen, the Netherlands.
5
University of Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands.
6
Palm Beach Atlantic University, Lloyd L. Gregory School of Pharmacy, Department of Pharmaceutical Sciences, West Palm Beach, FL, USA.
7
Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.

Abstract

COPD is characterized by persistent airflow limitation, neutrophilia and oxidative stress from endogenous and exogenous insults. Current COPD therapy involving anticholinergics, β2-adrenoceptor agonists and/or corticosteroids, do not specifically target oxidative stress, nor do they reduce chronic pulmonary inflammation and disease progression in all patients. Here, we explore the effects of Sul-121, a novel compound with anti-oxidative capacity, on hyperresponsiveness (AHR) and inflammation in experimental models of COPD. Using a guinea pig model of lipopolysaccharide (LPS)-induced neutrophilia, we demonstrated that Sul-121 inhalation dose-dependently prevented LPS-induced airway neutrophilia (up to ~60%) and AHR (up to ~90%). Non-cartilaginous airways neutrophilia was inversely correlated with blood H2S, and LPS-induced attenuation of blood H2S (~60%) was prevented by Sul-121. Concomitantly, Sul-121 prevented LPS-induced production of the oxidative stress marker, malondialdehyde by ~80%. In immortalized human airway smooth muscle (ASM) cells, Sul-121 dose-dependently prevented cigarette smoke extract-induced IL-8 release parallel with inhibition of nuclear translocation of the NF-κB subunit, p65 (each ~90%). Sul-121 also diminished cellular reactive oxygen species production in ASM cells, and inhibited nuclear translocation of the anti-oxidative response regulator, Nrf2. Our data show that Sul-121 effectively inhibits airway inflammation and AHR in experimental COPD models, prospectively through inhibition of oxidative stress.

PMID:
27229886
PMCID:
PMC4882609
DOI:
10.1038/srep26928
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center