title: Hypoxic preconditioning with cobalt attenuates hypobaric hypoxia-induced oxidative damage in rat lungs.
abstract: Shukla, Dhananjay, Saurabh Saxena, Purushotman Jayamurthy, Mustoori Sairam, Mrinalini, Singh, Swatantra Kumar Jain, Anju Bansal, and Govindaswamy Ilavazaghan. High Alt. Med. Biol. 10:57-69, 2009.-Hypoxic preco759nditioning (HPC) provides robust protection against injury from subsequent prolonged hypobaric hypoxia, which is a characteristic of high altitude and is known to induce oxidative injury in lung by increasing the generation of reactive oxygen species (ROS) and decreasing the effectiveness of the antioxidant defense system. We hypothesize that HPC with cobalt might protect the lung from subsequent hypobaric hypoxia-induced lung injury. HPC with cobalt can be achieved by oral feeding of CoCl(2) (12.5 mg kg(-1)) in rats for 7 days. Nonpreconditioned rats responded to hypobaric hypoxia (7619 m) by increased reactive oxygen species (ROS) generation and a decreased GSH/GSSG ratio. They also showed a marked increase in lipid peroxidation, heat-shock proteins (HSP32, HSP70), metallothionins (MT), levels of inflammatory cytokines (TNF-alpha, IFN-gamma, MCP-1), and SOD, GPx, and GST enzyme activity. In contrast, rats preconditioned with cobalt were far less impaired by severe hypobaric hypoxia, as observed by decreased ROS generation, lipid peroxidation, and inflammatory cytokine release and an inceased GSH/GSSG ratio. Increased expression of antioxidative proeins Nrf-1, HSP-32, and MT was also observed in cobalt- preconditioned animals. A marked increase in the protein expression and DNA binding activity of hypoxia-inducible transcriptional factor (HIF-1alpha) and its regulated genes, such as erythropoietin (EPO) and glucose transporter-1 (glut-1), was observed after HPC with cobalt. We conclude that HPC with cobalt enhances antioxidant status in the lung and protects from subsequent hypobaric hypoxia-induced oxidative stress.
authors.affiliation: Defence Institute of Physiology & Allied Sciences, Defence Research and Development Organization, Timarpur, Delhi, India.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Shukla
authors.forename: Saurabh
authors.initials: S
authors.lastname: Saxena
authors.forename: Purushotman
authors.initials: P
authors.lastname: Jayamurthy
authors.forename: Mustoori
authors.initials: M
authors.lastname: Sairam
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Singh
authors.forename: Swatantra Kumar
authors.initials: SK
authors.lastname: Jain
authors.forename: Anju
authors.initials: A
authors.lastname: Bansal
authors.forename: Govindaswamy
authors.initials: G
authors.lastname: Ilavazaghan
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D003035:Cobalt / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D019803:Glutathione Disulfide / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D055370:Lung Injury / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051265:NF-E2-Related Factor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016587:Antimutagenic Agents; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051265:NF-E2-Related Factor 1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; D008668:Metallothionein; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; C018021:cobaltous chloride; D005978:Glutathione; D019803:Glutathione Disulfide