Inhibition of oxidative stress by apocynin attenuated COPD progression
and vascular injury by cigarette smoke exposure
Background and Purpose: Cardiovascular disease (CVD) affects up to half
of the patients with chronic obstructive pulmonary disease (COPD), which
exerts 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 CVD.
Experimental Approach: Male BALB/c mice were exposed to either room air
(Sham) or cigarette smoke (CS) generated from 9 cigarettes per day, 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) activity against the oxidative insults of CS exposure.
These preservative effects were maintained up until the 24-week time
point. 24-week of apocynin treatment exhibited marked benefits on airway
inflammation (reduced infiltration of macrophage, neutrophil and
lymphocyte) and lung function decline (hyperinflation), and prevented
airway collagen deposition by CS exposure. Conclusion and Implications:
Limiting NOX activity may slow COPD progression and lower CVD risk,
particularly when signs of oxidative stress become evident.