Prophylactic Administration of Curcumin Abates the Incidence of Hypobaric Hypoxia Induced Pulmonary Edema in Rats: A Molecular Approach

Abstract

Background and purpose: High Altitude Pulmonary Edema (HAPE) is a severe high altitude illness with serious pulmonary manifestations. The present study reports benefits of prophylactic administration of curcumin in prevention of hypoxia induced pulmonary edema. Experimental approach: Male Sprague Dawley rats (n=6 per group) were exposed to a stimulated hypobaric hypoxia at 7620 m for 6 h. The groups studied were (I) Normoxia, (II) Hypoxia (6 h), (III) Normoxia+curcumin (50 mg/kg BW) and (IV) Hypoxia+curcumin (50 mg/kg BW). Curcumin at 50 mg/kg BW, given orally 1 h prior to hypoxia exposure was considered from dose dependent studies as the optimum dose, due to significant reduction in the level of lung water content and lung transvascular leakage (p<0.001) as compared to control (6 h hypoxia). Biochemical analysis, vascular leakage studies, differential expression of proteins were determined by ELISA, Western Blotting and Immunohistochemistry. Changes in lung parenchyma were evaluated by histopathology. Results: Curcumin administration (50 mg/kg BW) to rats, 1 h prior to hypoxic exposure showed a significant decrease in lactate dehydrogenase (LDH), albumin extravasation in broncho-alveolar lavage (BAL) fluid, oxidative stress (ROS and MDA) levels along with concomitant increase in antioxidant status (GSH, GPx and SOD) in lungs of rats compared to control. Curcumin significantly attenuated the IKKαβ , IKBβ there by leading to down regulation of NFκB protein levels and their downstream regulatory genes (pro-inflammatory cytokines and cell adhesion molecules). Further, hypoxia enhanced HIF-1α and VEGF levels in lungs were significantly down regulated by curcumin leading to reduction in vascular leakage in lungs of rats under hypoxia over control (Hypoxia). The histopathological observations provide substantial evidence in reduction of edema and inflammation by curcumin treatment. Conclusion: These results indicate that, curcumin to be a potent drug against HAPE as it effectively attenuates inflammation as well as fluid influx in the lungs of rats under hypoxia.