Quercetin attenuates the hyperoxic lung injury in neonatal mice: Implications for Bronchopulmonary dysplasia (BPD)

Food Chem Toxicol. 2018 Apr;114:23-33. doi: 10.1016/j.fct.2018.02.026. Epub 2018 Feb 9.

Abstract

Quercetin (QU) is one of the most common flavonoids that are present in a wide variety of fruits, vegetables, and beverages. This compound possesses potent anti-inflammatory and anti-oxidant properties. Supplemental oxygen is routinely administered to premature infants with pulmonary insufficiency. However, hyperoxia is one of the major risk factors for the development of bronchopulmonary dysplasia (BPD), which is also termed chronic lung disease in premature infants. Currently, no preventive approaches have been reported against BPD. The treatment of BPD is notably limited to oxygen administration, ventilatory support, and steroids. Since QU has been shown to be effective in reducing inflammation and oxidative stress in various disease models, we hypothesized that the postnatal QU treatment of newborn mice will protect against hyperoxic lung injury by the upregulation of the phase I (CYP1A/B) and/or phase II, NADPH quinone reductase enzymes. Newborn C57BL/6J mice within 24 h of birth with the nursing dams were exposed to either 21% O2 (air) and/or 85% O2 (hyperoxia) for 7 days. The mice were treated, intraperitoneally (i.p.) once every other day with quercetin, at a concentration of 20 mg/kg, or saline alone from postnatal day (PND) 2-6. The mice were sacrificed on day 7, and lung and liver tissues were collected. The expression levels of CYP1A1, CYP1B1, NQO1 proteins and mRNA as well as the levels of MDA-protein adducts were analyzed in lung and liver tissues. The findings indicated that QU attenuated hyperoxia-mediated lung injury by reducing inflammation and improving alveolarization with decreased number of neutrophil and macrophage infiltration. The attenuation of this lung injury correlated with the upregulation of CYP1A1/CYP1B1/NQO1 mRNA, proteins and the down regulation of NF-kB levels and MDA-protein adducts in lung and liver tissues. The present study demonstrated the potential therapeutic value of quercetin in the prevention and/or treatment of BPD.

Keywords: Bronchopulmonary dysplasia; Hyperoxia; Newborns; Oxidative stress and lung injury; Quercetin.

MeSH terms

  • Animals
  • Animals, Newborn / metabolism
  • Bronchopulmonary Dysplasia / drug therapy*
  • Bronchopulmonary Dysplasia / genetics
  • Bronchopulmonary Dysplasia / metabolism
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP1B1 / genetics
  • Cytochrome P-450 CYP1B1 / metabolism
  • Humans
  • Hyperoxia / drug therapy*
  • Hyperoxia / genetics
  • Hyperoxia / metabolism
  • Infant, Newborn
  • Lung / drug effects
  • Lung / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Oxidative Stress / drug effects
  • Oxygen / metabolism
  • Quercetin / administration & dosage*

Substances

  • Quercetin
  • Cyp1b1 protein, mouse
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1B1
  • NAD(P)H Dehydrogenase (Quinone)
  • Nqo1 protein, mouse
  • Oxygen