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

Bing Han*, Wilfred J. Poppinga, Haoxiao Zuo, Annet B. Zuidhof, I. Sophie T. Bos, Marieke Smit, Pieter Vogelaar, Guido Krenning, Robert H. Henning, Harm Maarsingh, Andrew J. Halayko, Bernard van Vliet, Stef Stienstra, Adrianus Cornelis van der Graaf, Herman Meurs, Martina Schmidt

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

12 Citaten (Scopus)
277 Downloads (Pure)


COPD is characterized by persistent airflow limitation, neutrophilia and oxidative stress from endogenous and exogenous insults. Current COPD therapy involving anticholinergics, beta(2)-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 similar to 60%) and AHR (up to similar to 90%). Non-cartilaginous airways neutrophilia was inversely correlated with blood H2S, and LPS-induced attenuation of blood H2S (similar to 60%) was prevented by Sul-121. Concomitantly, Sul-121 prevented LPS-induced production of the oxidative stress marker, malondialdehyde by similar to 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-kappa B subunit, p65 (each similar to 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.

Originele taal-2English
Pagina's (van-tot)1-13
Aantal pagina's13
TijdschriftScientific Reports
StatusPublished - 27-mei-2016

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