Inhibition of oxidative stress by apocynin attenuated chronic obstructive pulmonary disease progression and vascular injury by cigarette smoke exposure

Abstract

Background and Purpose Cardiovascular disease affects up to half of the patients with chronic obstructive pulmonary disease (COPD), exerting deleterious impact on health outcomes and survivability. Vascular endothelial dysfunction marks the onset of cardiovascular disease. The present study examined the effect of a potent NADPH Oxidase (NOX) inhibitor and free‐radical scavenger, apocynin, on COPD‐related cardiovascular disease. Experimental Approach Male BALB/c mice were exposed to either room air (Sham) or cigarette smoke (CS) generated from 9 cigarettes·day−1, 5 days a week for up to 24 weeks with or without apocynin treatment (5 mg·kg−1·day−1, intraperitoneal injection). Key Results Eight‐weeks of apocynin treatment reduced airway neutrophil infiltration (by 42%) and completely preserved endothelial function and endothelial nitric oxide synthase (eNOS) availability against the oxidative insults of cigarette smoke exposure. These preservative effects were maintained up until the 24‐week time point. 24‐week of apocynin treatment markedly reduced airway inflammation (reduced infiltration of macrophage, neutrophil and lymphocyte), lung function decline (hyperinflation) and prevented airway collagen deposition by cigarette smoke exposure. Conclusion and Implications Limiting NOX activity may slow COPD progression and lower cardiovascular disease risk, particularly when signs of oxidative stress become evident.

Cigarette Smoke-Induced Respiratory Response: Insights into Cellular Processes and Biomarkers

“…Xinjing et al reported that NOX 1, 4, and 5 were detected at various sites such as lung epithelial cells, vascular endothelial cells, and macrophages, and NOX2 was mainly detected in lung macrophages and neutrophils [ 214 ]. Stanley et al also reported that the NOX inhibitor apocynin inhibited lung inflammation and vascular injury caused by oxidative stress in the CS-induced mouse model [ 215 ]. In addition, expression of NOX in COPD has been reported in several studies [ 216 , 217 , 218 ].…”