This Research Center of Excellence (RCE) entitled: """"""""Novel Treatments of Chlorine Induced Injury to the Cardio-Respiratory Systems"""""""" consists of three projects and two cores. The unifying theme spanning all projects is that exposure of animals to C12 results in the formation of reactive intermediates which deplete ascorbate and reduced glutathione in the lung epithelial fluids, damage key components of the respiratory and alveolar epithelial [such as transient receptor protein (TRP) and epithelial sodium channels (ENaC)] and then, via inhibition of eNOS signaling compromise seminal functions of the pulmonary and systemic vasculatures. Furthermore, we propose that these toxic effects of C12 will be heightened in animals infected with respiratory syncytial virus or challenged with ova albumin. In our first series of experiments we will perform a number of state of the art biochemical, biophysical, physiological and morphometric measurements in RSV infected and ova albumin challenged mice as well as normal rats prior to and following C12 exposure to document the onset and progression of injury to lung epithelia and pulmonary and systemic vasculature. We will then treat them with antioxidants, TRP antagonists, /32 agonists and nitrite administered at various intervals post C12 exposure either intra-tracheally or via aerosolization or intraperitoneally (antioxidants and nitrite) and quantify recovery by specific functional measurements. Strong points of the RCE include the diverse talents of the investigators, the unique facilities, and the novelty of the preliminary data. The three projects (two of which build on novel findings generated by existing UO1 grants) are supported by an administrative core and the exposure core, which play key roles by both providing essential functions (such as exposure of animals to C12) and helping to integrate the team into a cohesive entity.
| Song, Weifeng; Yu, Zhihong; Doran, Stephen F et al. (2015) Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness. Am J Physiol Lung Cell Mol Physiol 309:L205-10 |
| Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana et al. (2014) TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury. Am J Physiol Lung Cell Mol Physiol 307:L158-72 |
| Gessner, Melissa A; Doran, Stephen F; Yu, Zhihong et al. (2013) Chlorine gas exposure increases susceptibility to invasive lung fungal infection. Am J Physiol Lung Cell Mol Physiol 304:L765-73 |
| Li, Changzhao; Weng, Zhiping; Doran, Stephen F et al. (2013) Chlorine induces the unfolded protein response in murine lungs and skin. Am J Respir Cell Mol Biol 49:197-203 |
| Ambalavanan, Namasivayam; Stanishevsky, Andrei; Bulger, Arlene et al. (2013) Titanium oxide nanoparticle instillation induces inflammation and inhibits lung development in mice. Am J Physiol Lung Cell Mol Physiol 304:L152-61 |
| Zhao, Run-Zhen; Nie, Hong-Guang; Su, Xue-Feng et al. (2012) Characterization of a novel splice variant of ? ENaC subunit in human lungs. Am J Physiol Lung Cell Mol Physiol 302:L1262-72 |
| Bracher, Andreas; Doran, Stephen F; Squadrito, Giuseppe L et al. (2012) Targeted aerosolized delivery of ascorbate in the lungs of chlorine-exposed rats. J Aerosol Med Pulm Drug Deliv 25:333-41 |
| Fanucchi, Michelle V; Bracher, Andreas; Doran, Stephen F et al. (2012) Post-exposure antioxidant treatment in rats decreases airway hyperplasia and hyperreactivity due to chlorine inhalation. Am J Respir Cell Mol Biol 46:599-606 |
| Samal, Andrey A; Honavar, Jaideep; Brandon, Angela et al. (2012) Administration of nitrite after chlorine gas exposure prevents lung injury: effect of administration modality. Free Radic Biol Med 53:1431-9 |
| Filippidis, Aristotelis S; Zarogiannis, Sotirios G; Randich, Alan et al. (2012) Assessment of locomotion in chlorine exposed mice by computer vision and neural networks. J Appl Physiol 112:1064-72 |
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