Prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats

• Published in: PloS one Vol. 14; no. 6; p. e0219075
• Main Authors: Tripathi, Ankit, Kumar, Bhuvnesh, Sagi, Sarada S K
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.06.2019; Public Library of Science (PLoS)
• Subjects: Albumin; Animals; Antioxidants; Antioxidants (Nutrients); Antioxidants - pharmacology; Antioxidants - therapeutic use; Attenuation; Biochemical analysis; Biochemistry; Biology and Life Sciences; Bone morphogenetic proteins; Cell adhesion & migration; Cytokines; Cytokines - metabolism; Disease Models, Animal; Dosage and administration; Drug therapy; Dyspnea; Edema; Endothelial growth factors; Enzyme-linked immunosorbent assay; Exposure; Extravasation; GA-binding protein; Health aspects; Histochemistry; Histopathology; Hypoxia; Hypoxia - drug therapy; Hypoxia - metabolism; Inflammation; Intercellular adhesion molecule 1; Interleukin 4; Kinases; Laboratory rats; Leakage; Lipid Peroxidation - drug effects; Lung - drug effects; Lung - metabolism; Lungs; Male; Medical research; Medicine and Health Sciences; Moisture content; NF-kappa B - metabolism; NF-κB protein; Nutrition; Oxidative stress; Oxidative Stress - drug effects; P-selectin; Parenchyma; Physiology; Preconditioning; Prophylaxis; Pulmonary arteries; Pulmonary edema; Quercetin; Quercetin - pharmacology; Quercetin - therapeutic use; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reduction; Rodents; Supplementation; Supplements; Transforming growth factors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vascular endothelial growth factor; Water content; Western blotting; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0219075

The objective of the study was to find out the prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats. Male SD rats received different doses of quercetin @ 25mg, 50mg, 100mg and 200mg/Kg BW, 1h prior to hypobaric hypoxia exposure (7,620m, for 6h). Quercetin 50 mg/kg BW supplemented orally 1h prior to hypoxia exposure was considered to be the optimum dose, due to significant reduction (p<0.001) in lung water content and lung transvascular leakage compared to control (hypoxia, 6h). Further, biochemical analysis (ROS, MDA, GSH, GPx, LDH, and albumin) and differential expressions of proteins (IKK-α/β, NFĸB, Nrf-2,TNF-α, ICAM-1, VCAM, P-selectin, Hif-1α, VEGF, TNF-α, TGF-β, INF-γ and IL-4) were determined by western blotting and ELISA. Changes in lung parenchyma were assessed by histopathology. Quercetin (50 mg/kg BW) prophylaxis under hypoxia showed significant reduction in oxidative stress (ROS and MDA), concomitant increase in antioxidants (GSH, GPx and SOD) followed by decreased LDH and albumin extravasation in BAL fluid over hypoxia. Quercetin prophylaxis significantly down regulated hypoxia induced increase in IKKα/β and NFĸB expressions leading to reduction in the levels of pro-inflammatory cytokines (TNF-α and INF-γ) followed by up regulation of anti-inflammatory cytokines (IL-4 and INF-γ) in lungs. Further, hypoxia mediated increase in HIF-1α was stabilized and VEGF levels in lungs were significantly down regulated by quercetin supplementation, leading to reduction in vascular leakage in lungs of rats under hypoxia. However, Quercetin has also enacted as Nrf-2 activator which significantly boosted up the synthesis of GSH under hypoxic condition compared to hypoxia. Histopathological observations further confirmed that quercetin preconditioning has an inhibitory effect on progression of oxidative stress and inflammation via attenuation of NFκB and stabilization HIF-1α in lungs of rats under hypoxia.These studies indicated that quercetin prophylaxis abrogates the possibility of hypobaric hypoxia induced pulmonary edema in rats.