loading page

Ebselen reduces cigarette smoke-induced vascular endothelial dysfunction in mice
  • +4
  • Kurt Brassington,
  • Stanley Chan,
  • Huei Seow,
  • Aleksandar Dobric,
  • Steven Bozinovski,
  • Stavros Selemidis,
  • Ross Vlahos
Kurt Brassington
RMIT University

Corresponding Author:[email protected]

Author Profile
Stanley Chan
RMIT University
Author Profile
Huei Seow
RMIT University
Author Profile
Aleksandar Dobric
RMIT University
Author Profile
Steven Bozinovski
RMIT University
Author Profile
Stavros Selemidis
RMIT University
Author Profile
Ross Vlahos
RMIT University
Author Profile

Abstract

Background and Purpose: It is well established that both smokers and patients with COPD are at a significantly heightened risk of cardiovascular disease (CVD), although the mechanisms underpinning the onset and progression of comorbid CVD are largely unknown. Here, we explored whether cigarette smoke (CS) exposure impairs vascular function in mice and given the well-known pathological role for oxidative stress in COPD, whether the antioxidant compound ebselen prevents CS-induced vascular dysfunction in mice. Experimental Approach: Male BALB/c mice were exposed to either room air (sham) or CS generated from 9 cigarettes per day, 5 days a week for 8 weeks. Mice were treated with ebselen (10mg/kg, oral gavage once daily) or vehicle (5% w/v CM cellulose in water) 1 h prior to the first CS exposure of the day. Upon sacrifice, bronchoalveolar lavage fluid (BALF) was collected to assess pulmonary inflammation and the thoracic aorta was excised to investigate vascular endothelial and smooth muscle dilator responses ex-vivo. Key Results: CS exposure caused a significant increase in lung inflammation which was reduced by ebselen. CS also caused significant endothelial dysfunction in the thoracic aorta which was attributed to a downregulation of eNOS expression and increased vascular oxidative stress. Ebselen abolished the aortic endothelial dysfunction seen in CS-exposed mice by reducing the oxidative burden and preserving eNOS expression. Conclusion and Implications: Targeting CS-induced oxidative stress with ebselen may provide a novel means for treating the life-threatening pulmonary and cardiovascular manifestations associated with cigarette smoking and COPD.
03 Sep 2020Submitted to British Journal of Pharmacology
03 Sep 2020Submission Checks Completed
03 Sep 2020Assigned to Editor
09 Sep 2020Reviewer(s) Assigned
11 Nov 2020Review(s) Completed, Editorial Evaluation Pending
11 Nov 2020Editorial Decision: Revise Minor
21 Dec 20201st Revision Received
22 Dec 2020Submission Checks Completed
22 Dec 2020Assigned to Editor
22 Dec 2020Reviewer(s) Assigned
20 Jan 2021Editorial Decision: Accept