In Vivo Detection of Free Radical Generation

自由基产生的体内检测

• 批准号: 8734091
• 负责人: RONALD P MASON
• 金额: $ 62.66万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8734091
• 关键词: Animal Disease Models; Antibodies; Biochemical; Biochemical Pathway; Biological; Complex; Detection; Diesel Exhaust; Disease; Electron Microscopy; Endotoxins; Exotoxins; Free Radical Formation; Free Radicals; Generations; Human; Immune System Diseases; Immunity; In Vitro; Infection; Inflammation; Inflammatory; Investigation; Lipids; Lipopolysaccharides; Liquid substance; Lung; Lung Inflammation; Mediating; Mediator of activation protein; Metals; Methods; Obesity; Organ; Pathogenesis; Production; Pseudomonas aeruginosa; Reaction; Research Priority; Spin Trapping; Staphylococcal Enterotoxin B; Steatohepatitis; Sulfites; Superantigens; Techniques; Testing; Tissues; Toxic effect; Work; adduct; allergic response; disorder risk; environmental agent; in vivo; novel; particle; pathogen; response; toxic metal

We have set research priorities to focus on free radical generation in animal models of disease and toxicity for which there is a strong indication of an environmental component. The ways in which environmental agents increase disease risks and toxicity are still poorly understood. In the past our work has been concentrated on the in vivo formation and detection of free radicals from toxic metals and organic compounds and extended into investigations of free radical formation during inflammation caused by lipopolysaccharide itself and in combination with diesel exhaust particles. It is now continued into studies of environmental exotoxins and pathogens with the aim of understanding the basic free radical mechanisms involved in distinctive organ infections, immune disease, and obesity. In vivo spin trapping has been the most successful method for the detection of highly reactive free radical molecules in vivo. The group continued to use spin trapping to solve in vitro biochemical and in vivo toxicological disease problems by using two major approaches for spin trapping, with either ESR detection or antibody recognition and MS identification of the trapped radical. By the use of in vivo spin-trapping methods, these studies test the hypotheses that: 1) free radicals are causative molecules in the complex pathogenesis of lung infections, obesity and allergic response; and 2) specific biochemical pathways are involved in triggering generation of free radicals that may act as mediators and/or modulators of inflammatory reactions associated with human immunity and disease response. Free radical generation in vivo caused by the bacterial pathogen Pseudomonas aeruginosa, superantigen staphylococcal enterotoxin B, the endotoxin LPS, obesity, CCl4, and sulfites has been shown in specific states of lung inflammation, steatohepatitis, and allergic response.

我们已经确定了研究重点，重点是疾病和毒性的动物模型中的自由基生成，其中有强烈的环境成分的迹象。 环境因素增加疾病风险和毒性的方式仍然知之甚少。在过去，我们的工作一直集中在体内形成和检测的自由基从有毒金属和有机化合物，并扩展到自由基形成的调查过程中引起的炎症脂多糖本身，并结合柴油机尾气颗粒。 它现在继续研究环境外毒素和病原体，目的是了解参与独特器官感染，免疫疾病和肥胖症的基本自由基机制。 在体内自旋捕获已成为最成功的方法，用于检测高活性的自由基分子在体内。该小组继续使用自旋捕获来解决体外生物化学和体内毒理学疾病问题，通过使用两种主要的自旋捕获方法，ESR检测或抗体识别和MS鉴定捕获的自由基。 通过使用体内自旋捕获方法，这些研究测试了以下假设：1）自由基是肺部感染、肥胖和过敏反应的复杂发病机制中的致病分子;以及2）特定的生化途径参与触发自由基的产生，所述自由基可以充当与人体免疫和疾病反应相关的炎症反应的介质和/或调节剂。由细菌病原体铜绿假单胞菌、超抗原葡萄球菌肠毒素B、内毒素LPS、肥胖症、CCl 4和亚硫酸盐引起的体内自由基产生已在肺部炎症、脂肪性肝炎和过敏反应的特定状态中显示。