title: Nanocurcumin accords protection against acute hypobaric hypoxia induced lung injury in rats.
abstract: Decline in oxygen availability experienced under hypobaric hypoxia (HH) mediates imbalance in lung fluid clearance and is a causative agent of acute lung injury. Here, we investigate the pathological events behind acute HH mediated lung injury and assess the therapeutic efficacy of nanocurcumin in its amelioration. We assess the protective efficacy of nanotized curcumin (nanocurcumin) in ameliorating HH induced lung injury and compare to curcumin. Rats exposed to acute HH (6, 12, 24, 48 and 72 h) were subjected to histopathology, blood-gas analysis and clinical biochemistry, cytokine response and redox damage. HH induced lung injury was analysed using markers of lung injury due to pulmonary vasoconstriction (ET-1/2/3 and endothelin receptors A and B) and trans-vascular fluid balance mediator (Na+/K+ ATPase). The protective efficacy of nanocurcumin was analysed by examination of Akt/Erk signalling cascade by western blot. HH induced lung injury was associated with discrete changes in blood analytes, differential circulatory cytokine response and severe pulmonary redox damages. Up-regulation of ET-1/2/3 and its receptors along with down-regulation of Na+/K+ ATPase confirmed defective pulmonary fluid clearance which promoted edema formation. Nanocurcumin treatment prevented lung edema formation and restored expression levels of ET-1/2/3 and its receptors while restoring the blood analytes, circulatory cytokines and pulmonary redox status better than curcumin. Modulation in Akt/Erk signalling pathway in rat lungs under HH confirmed the protective efficacy of nanocurcumin.
authors.affiliation: Experimental Biology Division, Department of Experimental Biology, Defence Institute of Physiology and Allied Science, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi-54, India.
authors.forename: Sarita
authors.initials: S
authors.lastname: Nehra
authors.affiliation: Experimental Biology Division, Department of Experimental Biology, Defence Institute of Physiology and Allied Science, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi-54, India.
authors.forename: Varun
authors.initials: V
authors.lastname: Bhardwaj
authors.affiliation: Experimental Biology Division, Department of Experimental Biology, Defence Institute of Physiology and Allied Science, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi-54, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.affiliation: Experimental Biology Division, Department of Experimental Biology, Defence Institute of Physiology and Allied Science, Defence Research and Development Organization, Lucknow Road, Timarpur, New Delhi-54, India. deepika_saras@yahoo.com.
authors.forename: Deepika
authors.initials: D
authors.lastname: Saraswat
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D019333:Endothelin-2 / Q000235:genetics / Q000378:metabolism; D019334:Endothelin-3 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D049329:Nanostructures / Q000737:chemistry / Q000627:therapeutic use*; D010084:Oxidation-Reduction / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D019333:Endothelin-2; D019334:Endothelin-3; D020011:Protective Agents; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000254:Sodium-Potassium-Exchanging ATPase; D003474:Curcumin
keywords: Hypoxia; Lung injury; Nanocurcumin; Vasoconstriction