An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity.
An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity.
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DOI：
10.1016/j.jacbts.2016.10.006
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发表时间：
2017-02-01
期刊：
影响因子：
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通讯作者：
Jensen, Brian C
中科院分区：
文献类型：
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作者：
Beak, JuYoun;Huang, Wei;Jensen, Brian C
alpha 1A-ARs在心脏中发挥适应和保护作用。Dabuzalgron是一种口服选择性α 1A-AR激动剂，在治疗尿失禁的多项临床试验中耐受良好，但从未用于治疗人类或动物模型中的心脏病。在这项研究中，我们给用DOX治疗的小鼠施用dabuzalgron，DOX是一种广泛使用的化疗剂，具有可导致HF的剂量限制性心脏毒性。Dabuzalgron保护免受DOX诱导的心脏毒性，可能是通过保护线粒体功能。这些结果表明，用耐受性良好的口服药物dabuzalgron激活心脏α 1A-AR可能代表了治疗HF的新方法。
alpha1A-ARs play adaptive and protective roles in the heart. Dabuzalgron is an oral selective alpha1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, we administered dabuzalgron to mice treated with DOX, a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to HF. Dabuzalgron protected against DOX-induced cardiotoxicity, likely by preserving mitochondrial function. These results suggest that activating cardiac alpha1A-ARs with dabuzalgron, a well-tolerated oral agent, might represent a novel approach to treating HF.