Background:Obese-asthmatics have worse asthma control and experience higher rates of healthcare utilization.Increasing body mass index in asthmatics has been associated with greater airway oxidative stress and dysfunctional mitochondria.Airways epithelial cells of obese asthmatics are more likely to have dysfunctional mitochondria that produce more reactive oxygen species (Winnica et al 2019) The antioxidant protein paraoxonase 2 (PON2) plays an important role in preventing mitochondrial-derived oxidative stress and could therefore have therapeutic potential in these patients.Flavonoid quercetin increases PON2 levels in human airways epithelial cells and prevent oxidative injury (Winnica et al 2022) However the exact mechanism of such protective effects remains elusive.Nrf2 is an important regulator of cellular defense against oxidative stress.Our preliminary data show that quercetin increases the expression of Nfr2 with concomitant increases in PON2

Methods:Human bronchial epithelial cells were obtained from bronchoscopic brushings of asthmatics and controls. PON2 and Nfr2 protein were analyzed by Western blot, densitometry was performed for quantification.Quercetin was from Cayman Chemical Company

Result:Compared with untreated cells 25?M quercetin increases 50% of Nrf2 expression with a concomitant increase of PON2. Interestingly, compared with untreated cells, those treated with quercetin showed the highest increases in Nrf2 expression after exposure to the oxidant agent DMNQ

Conclusion:Increases in PON2 expression could be modulated by Nrf2 and potentially be a mechanism contributing to lessening the airway oxidative stress in obese asthmatics