A new antithrombotic agent, aspalatone, attenuated cardiotoxicity induced by doxorubicin in the mouse; possible involvement of antioxidant mechanism.
A new antithrombotic agent, aspalatone, attenuated cardiotoxicity induced by doxorubicin in the mouse; possible involvement of antioxidant mechanism.
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一种新型抗血栓药物阿斯帕拉酮可减轻多柔比星对小鼠的心脏毒性；
DOI：
10.1016/s0024-3205(96)00637-6
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发表时间：
1996
期刊：
影响因子：
6.1
通讯作者：
H. Kim
中科院分区：
文献类型：
--
作者：
C. Kim;S. Nam;D. Choi;J. Choi;E. Park;W. Jhoo;H. Kim
以乙酰水杨酸（ASP）和麦芽酚（MAL）为原料，合成了一种新型抗血栓药物阿帕拉通（APT;乙酰水杨酸麦芽酚酯）。表明APT具有体外抗氧化作用。为了评估APT在体内的假定抗氧化作用，我们开发了多柔比星（DOX）相关的心脏损伤，这可能与氧化应激有关。维生素E（Vit E）作为抗氧化剂的实例包括在本研究中。APT、MAL和Vit E长期给药可显著降低DOX多次给药（3 mg/kg × 4）动物的死亡率。APT、MAL和Vit E对DOX损伤的潜在作用可能是通过诱导谷胱甘肽过氧化物酶活性并抑制脂质过氧化来解释的。APT、MAL和维生素E的长期治疗也消除了DOX心肌病的组织病理学证据。而ASP对DOX所致的死亡率、心肌损伤及抗氧化损伤无明显影响。因此，APT对DOX心脏毒性的保护作用与Vit E相当。APT的抗氧化作用对DOX引起的心脏毒性副作用具有保护作用。
A new antithrombotic agent, aspalatone (APT; acetyl salicylic acid maltol ester), was synthesized by esterification of acetyl salicylic acid (ASP) and maltol (MAL). It was suggested that APT possessed an antioxidant effect in in vitro. To evaluate the putative antioxidant effect of APT in in vivo, we developed doxorubicin (DOX)-related cardiac damage, which might be implicated by oxidative stress. Vitamin E (Vit E) was included in the present study as an example of an antioxidant. Prolonged treatments with APT, MAL and Vit E significantly reduced the mortality in animals receiving multiple dose of DOX (3 mg kg × 4). The potential role of APT, MAL and Vit E against DOX insult may be explained by the induction of glutathione peroxidase activity accompanied by the inhibition of lipid peroxidation. Prolonged treatments of APT, MAL and Vit E also ablated histopathological evidence of DOX cardiomyopathy. ASP challenge, however, did not affect the mortality, myocardial lesion and antioxidant deficit induced by DOX treatments, In conclusion, the protective effect of APT was equipotent to that of Vit E against DOX cardiotoxicity. The results also suggest that the antiperoxidative effect of APT plays a protective role in DOX-related cardiotoxic side effect.
阿霉素对小鼠肝脏、心脏和肠道毒性的生化决定因素。
影响因子：
5.8
作者：
Odom,AL;Hatwig,CA;Stanley,JS;Benson,AM
通讯作者：
Benson,AM