Carvedilol-Afforded Protection against Daunorubicin-Induced Cardiomyopathic Rats In Vivo: Effects on Cardiac Fibrosis and Hypertrophy.
Carvedilol-Afforded Protection against Daunorubicin-Induced Cardiomyopathic Rats In Vivo: Effects on Cardiac Fibrosis and Hypertrophy.
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DOI：
10.5402/2011/430549
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Suzuki K
中科院分区：
文献类型：
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作者：
Arozal W;Sari FR;Watanabe K;Arumugam S;Veeraveedu PT;Ma M;Thandavarayan RA;Sukumaran V;Lakshmanan AP;Kobayashi Y;Mito S;Soetikno V;Suzuki K
蒽环类药物是最有效的抗癌药物，但其心脏毒性作用可能与氧化应激有关。卡维地洛是第三代非选择性β-肾上腺素受体拮抗剂，具有清除活性氧和抑制活性氧的双重作用。它通过减少氧化应激和细胞凋亡对柔红霉素（DNR-）诱导的心脏毒性具有保护作用。本研究旨在观察卡维地洛对DNR诱导的心肌病大鼠左室功能、心肌纤维化和肥厚的影响。卡维地洛可提高存活率，预防收缩和舒张功能障碍，减轻心肌纤维化和肥大。与对照组相比，DNR单独治疗组大鼠心肌ANP、PKC-α、OPN和TGF-β1表达上调，加塔-4表达下调，卡维地洛治疗组可显著逆转上述变化。本研究的结果增加了卡维地洛与蒽环类药物联合使用时的心脏保护作用的现有证据，并解释了两者联合使用的潜在机制。
Anthracyclines, most powerful anticancer agents, suffer from their cardiotoxic effects, which may be due to the induction of oxidative stress. Carvedilol, a third-generation, nonselective β-adrenoreceptor antagonist, possesses both reactive oxygen species (ROS) scavenging and ROS suppressive effects. It showed protective effects against daunorubicin- (DNR-) induced cardiac toxicity by reducing oxidative stress and apoptosis. This study therefore was designed to examine the effects of carvedilol on DNR-induced cardiomyopathic rats, focused on the changes of left ventricular function, cardiac fibrosis, and hypertrophy. Carvedilol increased survival rate, prevented systolic and diastolic dysfunction, and attenuated myocardial fibrosis and hypertrophy. DNR alone treated rats showed upregulated myocardial expression of ANP, PKC-α, OPN, and TGF-β1 and downregulation of GATA-4 in comparison with control, and treatment with carvedilol significantly reversed these changes. The results of the present study add the available evidences on the cardioprotection by carvedilol when associated with anthracyclines and explain the mechanisms underlying the benefits of their coadministration.