Department of Cardiology, Shangqiu No 1 People's Hospital, Shangqiu, Henan, China.
Environ Toxicol. 2019 May;34(5):645-651. doi: 10.1002/tox.22730. Epub 2019 Feb 7.
Doxorubicin (DOX)-induced cardiomyopathy is a lethal disease. DOX-induced cardiotoxic effects are attributed towards increased redox status and apoptotic signaling. In this study, we show that genistein offers protection against DOX-induced cardio toxicity in the mice model. DOX-mediated increase in serum cardiac troponin and redox markers (ROS, LPO, 4-hydroxynonenal-protein adducts [HNE] levels) was significantly reduced by genistein treatment. Significantly increased TNF-α, IL-6, IL-8 expressions during DOX-induced inflammatory responses were down regulated by genistein treatment. Further, we found that genistein regulated antioxidant response through increased Nrf-2, HO-1, NQO1 protein expressions. In addition, DOX downregulated survival proteins (p-Akt, Bcl-2) with concomitant upregulation in Erk (1/2), Bax and cleaved caspase-3 expressions. The apoptotic activation was significantly downregulated by genistein treatment through suppression of apoptosis. Altogether, these findings show that genistein protects against DOX-induced cardiotoxic effects through activation of Nrf-2/HO-1 signaling.
阿霉素（DOX）诱导的心肌病是一种致命的疾病。DOX 诱导的心脏毒性作用归因于氧化还原状态和凋亡信号的增加。在本研究中，我们表明染料木黄酮可在小鼠模型中提供针对 DOX 诱导的心脏毒性的保护。染料木黄酮处理可显著降低 DOX 介导的血清心肌肌钙蛋白和氧化还原标志物（ROS、LPO、4-羟基壬烯醛蛋白加合物[HNE]水平）的增加。染料木黄酮处理可下调 DOX 诱导的炎症反应中 TNF-α、IL-6、IL-8 的表达。此外，我们发现染料木黄酮通过增加 Nrf-2、HO-1、NQO1 蛋白表达来调节抗氧化反应。此外，DOX 下调存活蛋白（p-Akt、Bcl-2），同时上调 Erk（1/2）、Bax 和 cleaved caspase-3 的表达。通过抑制细胞凋亡，染料木黄酮处理可显著下调细胞凋亡的激活。总之，这些发现表明，染料木黄酮通过激活 Nrf-2/HO-1 信号通路来保护免受 DOX 诱导的心脏毒性作用。
