TREATMENT OF BPD USING MIMETICS OF SUPEROXIDE DISMUTASE

使用超氧化物歧化酶模拟物治疗 BPD

• 批准号: 7716049
• 负责人: James D Crapo
• 金额: $ 2.26万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716049
• 关键词: Animal Model; Chronic lung disease; Class; Computer Retrieval of Information on Scientific Projects Database; Cultured Cells; Disease; Drug Kinetics; Extracellular Space; Funding; Goals; Grant; Injury; Institution; Lead; Lung; Modeling; Newborn Respiratory Distress Syndrome; Oxidative Stress; Oxygen; Papio; Pathogenesis; Porphyrins; Premature Infant; Research; Research Personnel; Resources; Role; Source; Superoxide Dismutase; Superoxides; Survivors; Testing; Tissues; Toxic effect; United States National Institutes of Health; catalase; design; free radical oxygen; insight; mimetics; novel; novel therapeutics; pressure

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. High concentrations of oxygen and increased airway pressure are administered to most preterm neonates with respiratory distress syndrome. Among the survivors, 20 percent to 30 percent develop a form of chronic lung disease called bronchopulmonary dyplasia (BPD). Tissue damage caused by the superoxide anion (O2-) and other free oxygen radicals has been implicated in the pathogenesis of BPD. We have synthesized a class of novel, small Mn(III) porphyrin mimetics of superoxide dismutase (SOD) and catalase. These compounds have been shown to be effective in blocking injury in cell culture and whole animal models of oxidative stress. Preliminary results now suggest that these SOD mimetics will be efficacious in protecting against the oxidative stress component of BPD in premature infants. We propose designing, synthesizing, and characterizing Mn(III)-porphyrins with high SOD activity that can be delivered to critical targets located in the intracellular and extracellular spaces of the lung. The efficacy of the new SOD mimetics will be tested on BPD through use of the Bronchopulmonary Resource Center in San Antonio. Our specific goals in this proposal are to 1) determine the pharmacokinetic/toxicity profiles of our existing lead SOD mimetics; 2) design and develop new SOD mimetics; 3) screen new SOD mimetics in nonprimate models of oxidative injury; 4) test SOD mimetics in baboon BPD; and, 5) determine the mode of action of SOD mimetics in the BPD model. We expect these studies to provide new insights on the role of oxidative stress in BPD and to provide a novel new therapeutic approach to reduce the impact of this devastating disease in premature infants.

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