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.