Ebselen reduces cigarette smoke‐induced endothelial dysfunction in mice

• DOI: 10.1111/bph.15400
• Publication Date: 2021-02-02T08:34:53Z
• Authors: Kurt Brassington; Stanley M. H. Chan; Huei Jiunn Seow; Aleksandar Dobric; Steven Bozinovski; Stavros Selemidis; Ross Vlahos
• Keywords: Ebselen; Endothelial Dysfunction; Dilator; Thoracic aorta

Background and Purpose It is well established that both smokers patients with COPD are at a significantly heightened risk of cardiovascular disease (CVD), although the mechanisms underpinning onset progression co‐morbid CVD largely unknown. Here, we explored whether cigarette smoke (CS) exposure impairs vascular function in mice given well‐known pathological role for oxidative stress COPD, antioxidant compound ebselen prevents CS‐induced dysfunction mice. Experimental Approach Male BALB/c were exposed to either room air (sham) or CS generated from nine cigarettes per day, 5 days week 8 weeks. Mice treated (10 mg·kg −1 , oral gavage once daily) vehicle (5% w/v CM cellulose water) 1 h prior first day. Upon killing, bronchoalveolar lavage fluid (BALF) was collected assess pulmonary inflammation, thoracic aorta excised investigate endothelial smooth muscle dilator responses ex vivo. Key Results caused significant increase lung inflammation which reduced by ebselen. also attributed down‐regulation eNOS expression increased stress. Ebselen abolished aortic seen CS‐exposed reducing burden preserving expression. Conclusion Implications Targeting may provide novel means treating life‐threatening manifestations associated smoking COPD.