Abstract
BackgroundObesity in asthmatics has been associated with higher airway oxidative stress in which dysfunctional mitochondria are a potential contributing source of excess free radicals. Paraoxonase 2 (PON2) plays an important role in reducing mitochondrial-derived oxidative stress and could, therefore, have therapeutic potential in these patients.ObjectivesWe used primary human bronchial epithelial cells (HBECs) from asthmatics and healthy controls to evaluate: a) protein levels of Paraoxonase 2 and b) to test the potential protective effect of quercetin supplementation in cells under oxidative stress conditions.ResultsCompared to lean controls, obese asthmatics had significantly lower PON2 airway epithelial levels (respectively, 1.08 vs. 0.47 relative units normalized by GAPDH) (p-value < 0.006). Treating HBECs in vitro for 24 hrs. with 25μM quercetin significantly increased PON2 protein levels: 15.5 treated cells vs. 9.8 untreated cells (relative units normalized by GAPDH) (p value = 0.004). Notably, compared to untreated cells, quercetin supplementation reduces mitochondrial superoxide and hydrogen peroxide production on HBECs cells exposed to different oxidative stress triggers such as 1–2 Naphthoquinone (1–2 NQ) and hydrogen peroxide, suggesting that PON2 might play a protective role ameliorating oxidative injury on human airway epithelium.ConclusionCompared to lean controls, obese asthmatics have significantly reduced PON2 levels in airway epithelial cells. Treatment with quercetin in vitro increased PON2 protein levels and prevented oxidative stress from different types of stimuli. Hence, quercetin supplementation may be a potential therapeutic strategy to prevent obesity-mediated airway oxidative stress in obese asthmatics.
Highlights
In patients with asthma, obesity and weight gain have been associated with increased asthma severity, which is a significant public health problem, given that nearly 40% of asthmatics in the United States are obese [1]
Obese asthmatics had significantly lower Paraoxonase 2 (PON2) airway epithelial levels (p-value < 0.006)
Treating Human Bronchial Epithelial Cells (HBECs) in vitro for 24 hrs. with 25μM quercetin significantly increased PON2 protein levels: 15.5 treated cells vs. 9.8 untreated cells (p value = 0.004)
Summary
Obesity and weight gain have been associated with increased asthma severity, which is a significant public health problem, given that nearly 40% of asthmatics in the United States are obese [1]. Mitochondrial dysfunction has been shown to contribute to airway oxidative stress, which could explain why inhaled corticosteroid lack efficacy in this subgroup of patients [2–6]. Mitochondrial-derived oxidative reactive oxygen species (mtROS) are generated during the transportation of electrons in the tricarboxylic acid cycle. Small amounts of reactive oxygen species (ROS) that leak out from the mitochondrial electron transport chain (ETC) can be generally handled by cellular defense mechanisms [11– 14]. Under pathologic conditions, such as asthma and obesity, antioxidant defense mechanisms may not be sufficient to prevent increased mtROS from injuring the cell and further worsening mitochondrial dysfunction. Obesity in asthmatics has been associated with higher airway oxidative stress in which dysfunctional mitochondria are a potential contributing source of excess free radicals.
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