Novel Treatments of Acrolein-induced Cardiotoxicity

丙烯醛引起的心脏毒性的新疗法

• 批准号: 8610016
• 负责人: Daniel Joseph Conklin
• 金额: $ 37.5万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-24 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8610016
• 关键词: 1 year old; 2-butenal; Accounting; Acrolein; Acute; Adult; Adverse effects; Age; Animals; Arthritis; Asthma; Autonomic nervous system; Biocide; Blood Pressure; Breathing; C57BL/6 Mouse; Calcium; Cardiac; Cardiopulmonary; Cardiotoxicity; Cardiovascular system; Chemical Warfare; Chemicals; Chronic; Clinical; Dermal; Development; Diesel Exhaust; Dose; Dyslipidemias; Echocardiography; Edema; Emergency Situation; Evaluation; Event; Exposure to; Extravasation; Eye; FDA approved; Female; Fire - disasters; Formaldehyde; Foundations; Gases; Goals; Heart; Herbicides; Human; Hydra Polyps; Industry; Inflammation; Injection of therapeutic agent; Injury; Intervention; Irrigation; Irritants; Lead; Lung; Measures; Mediating; Monitor; Mucins; Natural Disasters; Neurons; Nose; Oils; Pain; Pesticides; Pharmaceutical Preparations; Phase; Plasma; Production; Relative (related person); Route; Safety; Shipping; Ships; Signal Transduction; Skin; Structure of parenchyma of lung; System; TRPA1 Channel; TRPV1 gene; Testing; Therapeutic; Therapeutic Intervention; Toxic effect; Translational Research; Troponin I; Water; activin A; atherogenesis; capsazepine; carbonyl compound; combat; effective intervention; effectiveness measure; efficacy testing; forest; human morbidity; human mortality; improved; inhibitor/antagonist; insight; irritation; male; member; novel; older women; preclinical study; preconditioning; prevent; public health relevance; receptor; respiratory; response; sex

Novel Treatments of Acrolein-induced Cardiotoxicity The overall goal of this project is to develop new and improved countermeasures and therapeutics for preventing human mortality and morbidity associated with chemical threats. Such threats might be imposed by a terrorist attack, accidental leakage of chemicals used in industrial production, or those released during natural disasters and fires. The most common and abundant reactive chemicals, relevant to all these situations are reactive carbonyl compounds (RCCs). A prototypical member of this class is acrolein. Acrolein and related RCCs are the most abundant and toxic constituents generated in lethal amounts (600 ppm) during forest and structural fires. Profound respiratory and cardiovascular effects of exogenous and endogenous RCCs have also been described; however, neither the toxicological effects of RCCs nor their mechanisms of toxicity have been systematically delineated. Similarly, the specific vulnerability of young, old and women to RCC exposure has not been assessed. Most importantly, no effective countermeasures or therapeutic interventions are currently available. Possible therapeutic interventions include treatment with inhibitors of RCC receptors known as transient receptor potential (TRP) channels. These antagonists including TRPV1 and TRPA1 inhibitors hold promise to diminish the pain and inflammation in the cardiovascular and pulmonary systems associated with high dose exposure to RCC. Evaluation of mitigation therapies following high level RCC exposure will provide the first step in judging their relative efficacy for use in the case of a chemical emergency threat in humans.

丙烯醛致血管毒性的新治疗方法 该项目的总体目标是开发新的和改进的对策和治疗方法， 防止与化学品威胁有关的人类死亡和发病。这种威胁可能是由 恐怖袭击，工业生产中使用的化学品意外泄漏，或 自然灾害和火灾。与所有这些情况相关的最常见和最丰富的反应性化学物质 是反应性羰基化合物（RCC）。这类的典型成员是丙烯醛。丙烯醛及相关 RCCs是最丰富的有毒成分，在森林和森林中以致死量（600 ppm）产生， 结构性火灾外源性和内源性RCC对呼吸和心血管的影响深远， 然而，RCCs的毒理学效应及其毒性机制均未得到描述。 被系统地描绘出来。同样，年轻人、老年人和妇女对接触RCC的具体脆弱性 尚未评估。最重要的是，没有有效的对策或治疗干预措施， 目前可用。可能的治疗干预包括用已知的RCC受体抑制剂治疗。 瞬时受体电位（TRP）通道。这些拮抗剂包括TRPV1和TRPA1抑制剂， 承诺减少疼痛和炎症在心血管和肺部系统相关的 高剂量暴露于RCC。高水平RCC暴露后的缓解疗法评估将提供 这是判断它们在人类面临化学品紧急威胁时的相对功效的第一步。