Novel Treatments of Acrolein-induced Cardiotoxicity

丙烯醛心脏毒性的新治疗方法 这个项目的总体目标是开发新的和改进的对策和治疗方法 预防与化学威胁相关的人类死亡和发病率。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，或在 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活性化学物质 是活性羰基化合物(RCC)。这一类的典型成员是丙烯醛。丙烯醛及相关物质 RCC是森林和森林中产生的最丰富和最有毒的成分，致死量(600ppm) 结构性火灾。外源性和内源性RCCs对呼吸和心血管的深刻影响 然而，RCCs的毒理作用和它们的毒性机制都没有 都被系统地描绘出来了。同样，年轻人、老年人和妇女对RCC暴露的具体脆弱性 还没有经过评估。最重要的是，没有有效的对策或治疗干预措施 目前可用。可能的治疗干预措施包括使用已知的RCC受体抑制剂进行治疗 作为瞬时受体电位(Trp)通道。这些拮抗剂包括TRPV1和TRPA1抑制剂 承诺减少心血管和肺部系统的疼痛和炎症 高剂量接触肾细胞癌。对高水平RCC暴露后缓解疗法的评估将提供 判断它们在人类受到化学紧急威胁的情况下使用的相对有效性的第一步。

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.