Ebselen reduces cigarette smoke‐induced endothelial dysfunction in mice
| Autor: | Ross Vlahos, Stanley M H Chan, Steven Bozinovski, Stavros Selemidis, Huei Jiunn Seow, Kurt Brassington, Aleksandar Dobric |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Azoles
Male 0301 basic medicine antioxidant Isoindoles medicine.disease_cause Mice Pulmonary Disease Chronic Obstructive chemistry.chemical_compound 0302 clinical medicine cardiovascular disease Enos Organoselenium Compounds Smoke Thoracic aorta Endothelial dysfunction Lung Mice Inbred BALB C COPD medicine.diagnostic_test biology cigarette smoke Smoking vascular dysfunction Research Papers medicine.anatomical_structure Bronchoalveolar Lavage Fluid Research Paper medicine.medical_specialty endothelium Endothelium chronic obstructive pulmonary disease 03 medical and health sciences Internal medicine medicine.artery medicine Animals Humans Pharmacology business.industry Ebselen lung inflammation biology.organism_classification medicine.disease Mice Inbred C57BL 030104 developmental biology Bronchoalveolar lavage Endocrinology chemistry business 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | British Journal of Pharmacology |
| ISSN: | 1476-5381 0007-1188 |
| Popis: | 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 co-morbid 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 nine cigarettes per day, 5 days a week for 8 weeks. Mice were treated with ebselen (10 mg·kg-1 , 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 killing, 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 down-regulation 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |