The Cardiac Surgery Department, The First Hospital of Jilin University, Changchun, China.
School of Public Health, Jilin University, Changchun, China.
Cardiovasc Ther. 2017 Oct;35(5). doi: 10.1111/1755-5922.12277.
Doxorubicin (DOX) is an anthracycline antitumor drug. However, its clinical use is limited by dose-dependent cardiotoxicity and even progresses to chronic heart failure (CHF).
This study aims to investigate whether the Nrf2 activator, sulforaphane (SFN), can prevent DOX-induced CHF.
Male Sprague-Dawley rats which received treatment for 6 weeks were divided into four groups (n=30 per group): control, SFN, DOX and DOX plus SFN group.
Results revealed that DOX induced progressive cardiac damage as indicated by increased cardiac injury markers, cardiac inflammation, fibrosis and oxidative stress. SFN significantly prevented DOX-induced progressive cardiac dysfunction between 2-6 weeks and prevented DOX-induced cardiac function deterioration. Furthermore, it significantly decreased ejection fraction and increased the expression of brain natriuretic peptide. SFN also almost completely prevented DOX-induced cardiac oxidative stress, inflammation and fibrosis. SFN upregulated NF-E2-related factor 2 (Nrf2) expression and transcription activity, which was reflected by the increased mRNA expression of Nrf2 and its downstream genes. Furthermore, in cultured H9c2 cardiomyocytes, the protective effect of SFN against DOX-induced fibrotic and inflammatory responses was abolished by Nrf2 silencing.
We arrived at the conclusion that DOX-induced CHF can be prevented by SFN through the upregulation of Nrf2 expression and transcriptional function.
多柔比星（DOX）是一种蒽环类抗肿瘤药物。然而，其临床应用受到剂量依赖性心脏毒性的限制，甚至进展为慢性心力衰竭（CHF）。
本研究旨在探讨 Nrf2 激活剂，萝卜硫素（SFN）是否可以预防 DOX 诱导的 CHF。
雄性 Sprague-Dawley 大鼠接受 6 周治疗后分为四组（每组 n=30）：对照组、SFN 组、DOX 组和 DOX+SFN 组。
结果表明，DOX 诱导进行性心脏损伤，表现为心肌损伤标志物增加、心脏炎症、纤维化和氧化应激。SFN 可显著预防 DOX 诱导的 2-6 周进行性心脏功能障碍，并预防 DOX 诱导的心脏功能恶化。此外，它显著降低射血分数并增加脑钠肽的表达。SFN 还几乎完全预防 DOX 诱导的心脏氧化应激、炎症和纤维化。SFN 上调核因子 E2 相关因子 2（Nrf2）表达和转录活性，反映为 Nrf2 及其下游基因的 mRNA 表达增加。此外，在培养的 H9c2 心肌细胞中，SFN 对 DOX 诱导的纤维化和炎症反应的保护作用被 Nrf2 沉默所消除。
我们得出结论，SFN 通过上调 Nrf2 表达和转录功能可以预防 DOX 诱导的 CHF。
