Quercetin: a savior of alveolar barrier integrity under hypoxic microenvironment

Ankit Tripathi; Puja P Hazari; Anil K Mishra; Bhuvnesh Kumar; Sarada S K Sagi

doi:10.1080/21688370.2021.1883963

Quercetin: a savior of alveolar barrier integrity under hypoxic microenvironment

Tissue Barriers. 2021 Apr 3;9(2):1883963. doi: 10.1080/21688370.2021.1883963. Epub 2021 Feb 26.

Authors

Ankit Tripathi¹, Puja P Hazari², Anil K Mishra², Bhuvnesh Kumar¹, Sarada S K Sagi¹

Affiliations

¹ Hematology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur Delhi-India.
² Molecular Imaging and Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi-India.

Abstract

High altitude pulmonary edema (HAPE) is generally characterized by the loss of alveolar epithelial barrier integrity. The current study was undertaken to assess the noninvasive approaches of HAPE diagnosis and to evaluate the prophylactic potential of quercetin in preventing alveolar junction impairments. Male SD rats fed with quercetin 1 h prior to hypoxia (7,620 m, for 6 h) were selected. PET/CT imaging was performed to visualize the lung uptake of ¹⁸F-FDG in animals under hypoxia. Further, oxidant status, catalase activity, hematological & blood gas parameters were evaluated. Moreover, tight junction (TJ) proteins (ZO-1, JAM-C, Claudin-4, and occludin) expression analysis was accomplished using immune-blotting. The structural differences in lung epithelia were noted by TEM imaging. Quercetin prophylaxis has significantly reduced the FDG uptake in rat lungs under hypoxia. It has also dramatically alleviated the protein oxidation followed by an elevation in catalase activity in the lungs under hypoxia. The TJ protein expression in the lungs has also been restored to normal upon quercetin pre-treatment. Concomitantly, the quercetin preconditioning has elicited the stable blood gas and hematological parameters under hypoxia. The observations from TEM imaging have also implicated the normal lung epithelial structures in the quercetin pretreated animals under hypoxia. Quercetin prophylaxis has significantly restored alveolar epithelium integrity by abating oxidative stress in the lungs under hypoxia.Abbreviations: CT- Computed Tomography¹⁸F-FDG- Fluorodeoxyglucose (¹⁸FHAPE- High Altitude Pulmonary EdemaHb- HemoglobinHCT- HematocritHCO₃^- BicarbonateJAM- Junctional Adhesion MoleculeKBq- Killo BecquerelPaO₂- Partial pressure of arterial oxygenPaCO₂- Partial pressure of arterial carbon di-oxidePET- Positron Emission TomographyRBC- Red Blood CorpusclesSD- Sprague DawleyTJ- Tight JunctionsTEM- Transmission Electron MicroscopyWBC- White Blood CorpusclesZO- Zona Occludin.

Keywords: 18F-FDG; TJs; hape; oxidative stress; quercetin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alveolar Epithelial Cells / metabolism*
Cell Hypoxia / physiology*
Humans
Quercetin / metabolism*
Tumor Microenvironment / physiology*

Substances

Quercetin

Grants and funding

The study was conducted under the project entitled “Improving performance under different operational environments using suitable interventions” funded by the Defence Research and Development Organization, Government of India. Grant No.: DIP-265;DIPAS [DIP-265];