Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidative stress and apoptosis in mice
Baicalein alleviates doxorubicin-induced cardiotoxicity via suppression of myocardial oxidative stress and apoptosis in mice
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DOI：
10.1016/j.lfs.2015.11.018
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发表时间：
2016-01-01
期刊：
影响因子：
6.1
通讯作者：
Sistla, Ramakrishna
中科院分区：
文献类型：
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作者：
Sahu, Bidya Dhar;Kumar, Jerald Mahesh;Sistla, Ramakrishna
目的：阿霉素是一种广泛应用的蒽环类抗癌药物。不幸的是，阿霉素的临床使用具有心脏毒性的严重缺点。在这项研究中，我们研究了黄芩素，一种生物素，是否可以防止阿霉素诱导的心脏毒性在体内，我们描绘了可能的潜在mechanism.Main方法：雄性BALB/c小鼠腹腔阿霉素（15 mg/kg分为三个相等的剂量为15天）和/或口服黄芩素（25和50 mg/kg为15天）。结果：黄芩素能降低阿霉素诱导的血清肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、天门冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平的升高，并改善组织病理学损伤。黄芩素恢复了阿霉素诱导的酶和非酶心肌抗氧化剂的减少，并增加了核因子E2相关因子2（Nrf 2）和血红素加氧酶1（HO-1）的心肌表达。进一步研究表明，黄芩素可逆转Bax/Bcl-2比值，抑制阿霉素诱导的p53，切割caspase-3和PARP的表达，防止阿霉素诱导的DNA损伤。黄芩素处理还通过抑制I κ B α磷酸化和p65亚基的核转位来干扰阿霉素诱导的心肌NF-κ B信号传导。黄芩素处理的小鼠中阿霉素升高iNOS和亚硝酸盐水平也显著降低。然而，我们没有发现任何显着的变化（p > 0.05），在心肌TNF-α和IL-6的水平在控制和治疗animals.Significance：我们的发现表明，黄芩素可能是一个有前途的分子，用于预防阿霉素诱导的心脏毒性。(C)2015 Elsevier Inc. All rights reserved.
Aims: Doxorubicin is a widely used anthracycline derivative anticancer drug. Unfortunately, the clinical use of doxorubicin has the serious drawback of cardiotoxicity. In this study, we investigated whether baicalein, a bioflavonoid, can prevent doxorubicin-induced cardiotoxicity in vivo and we delineated the possible underlying mechanisms.Main methods: Male BALB/c mice were treated with either intraperitoneal doxorubicin (15 mg/kg divided into three equal doses for 15 days) and/or oral baicalein (25 and 50 mg/kg for 15 days). Serum markers of cardiac injury, histology of heart, parameters related to myocardial oxidative stress, apoptosis and inflammation were investigated.Key findings: Treatment with baicalein reduced doxorubicin-induced elevation of serum creatine kinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and ameliorated the histopathological damage. Baicalein restored the doxorubicin-induced decrease in both enzymatic and non-enzymatic myocardial antioxidants and increased the myocardial expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Further studies showed that baicalein could inverse the Bax/Bcl-2 ratio, suppress doxorubicin-induced p53, cleaved caspase-3 and PARP expression and prevented doxorubicin-induced DNA damage. Baicalein treatment also interferes with doxorubicin-induced myocardial NF-kappa B signaling through inhibition of I kappa B alpha phosphorylation and nuclear translocation of p65 subunit. Doxorubicin elevated iNOS and nitrites levels were also significantly decreased in baicalein treated mice. However, we did not find any significant change (p > 0.05) in the myocardial TNF-alpha and IL-6 levels in control and treated animals.Significance: Our finding suggests that baicalein might be a promising molecule for the prevention of doxorubicin-induced cardiotoxicity. (C) 2015 Elsevier Inc. All rights reserved.