Novel Treatments of Chlorine Induced Injury to the Cardio-Respiratory Systems-U54

氯引起的心肺系统损伤的新疗法-U54

• 批准号: 7932359
• 负责人: Sadis Matalon
• 金额: $ 2.5万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932359
• 关键词: Agonist; Albumins; Alveolar; Animals; Antioxidants; Arts; Biochemical; Centers of Research Excellence; Chlorine; Data; Epithelial; Epithelium; Exposure to; Grant; Injury; Liquid substance; Lung; Measurement; Mus; Nitrites; Ovum; Physiological; Play; Rattus; Recovery; Reduced Glutathione; Research Personnel; Respiratory System; Respiratory syncytial virus; Role; Seminal; Series; Signal Transduction; Sodium Channel; Talents; Toxic effect; ascorbate; epithelial Na+ channel; novel; pulmonary function; receptor; research study; respiratory

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：