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Specialized pro-resolving mediators as potential medical countermeasures in a pig model of chlorine gas-induced acute lung injury

专门的促解决介质作为氯气引起的急性肺损伤猪模型的潜在医学对策

基本信息

批准号：
10153787
负责人：
Satyanarayana Achanta
金额：
$ 24.15万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10153787
关键词：
Acute Lung Injury Air Airway Resistance Animal Disease Models Animal Model Anti-Inflammatory Agents Antidotes Antiinflammatory Effect Applications Grants Area Arthritis Attenuated Blood Blood Vessels CD59 Antigen Cardiopulmonary Chemical Injury Chemical Warfare Agents Chemical Weapons Chemicals Chlorine Colitis Data Development Docosahexaenoic Acids Eicosapentaenoic Acid Exposure to Extravasation Family suidae Fatty Acids Formulation Gases Generations Histopathology Hour Human Hydrochloric Acid Industrialization Inflammation Inflammatory Inflammatory Response Inhalant dose form Inhalation Injury Laboratories Lipids Lipoxins Literature Lung Maintenance Mediator of activation protein Mental Depression Methods Modeling Morbidity - disease rate Mus Mustard Gas Neutrophil Infiltration Omega-3 Fatty Acids Outcome Oxygen Paper Partial Pressure Pathway interactions Pharmacologic Substance Phase Physiological Plasma Process Recovery Reporting Research Resolution Respiratory System Review Literature Riots Rodent Sepsis Severities Signal Pathway Stimulus Structure of parenchyma of lung Sulfides Testing Therapeutic Therapeutic Agents Therapeutic Effect Tissues Translating Treatment Efficacy Vesicants Weight White Blood Cell Count procedure World War I analog animal rule asthma model chemical threat chlorine gas cytokine cytokine release syndrome healing improved indexing lipid mediator lipid metabolism liquid chromatography mass spectrometry lung injury medical countermeasure metabolomics methacholine mouse model novel porcine model pressure prevent primary endpoint receptor response tissue injury tissue repair water treatment

项目摘要

Chlorine is a highly utilized chemical in the U.S. with more than 10 million metric tons produced annually for purposes including water treatment, paper bleaching, and chemical manufacturing. Unfortunately, however, chlorine is also a toxic inhalant. Exposure to chlorine gas can cause immediate and sustained injury to the respiratory tract with the severity of injury depends on both concentration and duration of exposure. Whereas exposure to chlorine gas is typically accidental, it has been used as a chemical weapon since World War I. Despite its known chemical threat potencies since World War I, there is no specific antidote for chlorine gas-induced injuries. Recent studies in our laboratory revealed that post-exposure treatment with specialized pro-resolving mediators (SPMs), such as Resolvin D1 and Protectin D1 strongly improved lung injury outcomes in mice exposed to chlorine and hydrochloric acid (HCl). These SPMs are endogenous lipid derivatives produced during inflammation cascade that subsequently accelerates the resolution phase of inflammation. In the proposed grant application, we want to test these novel potential therapeutic agents in our well-established pig model of chlorine gas-induced acute lung injury following the FDA's animal rule.

在美国，氯是一种高度利用的化学品，产量超过1000万公吨。每年用于水处理、纸张漂白和化学制造。然而，不幸的是，氯也是一种有毒的吸入剂。接触氯气会导致呼吸道的即时和持续损伤，损伤的严重程度取决于浓度和暴露时间。然而，暴露于氯气通常由于是偶然的，它自第一次世界大战以来一直被用作化学武器。尽管其知名自第一次世界大战以来，化学威胁的效力，没有具体的解毒剂氯气引起的伤害。我们实验室最近的研究表明，暴露后用专门的促消退介质（SPM），如Resolvin D1和Protectin D1，暴露于氯和盐酸（HCl）的小鼠的损伤结果。这些SPM是在炎症级联过程中产生的内源性脂质衍生物，加速炎症的消退在拟议的拨款申请中，我们希望根据FDA的动物规则，在我们完善的氯气诱导的急性肺损伤猪模型中测试这些新的潜在治疗剂。