阿霉素 (Dox) 是一种经常用于治疗癌症的化疗药物，会引起心脏毒性，这种情况被称为 Dox 诱导的心脏毒性 (DIC)，而铁死亡在其病理生理学中起着重要作用。褐藻糖胶是一种具有多种生物活性和安全性的多糖，具有潜在的治疗和药物应用。本研究旨在探讨岩藻依聚糖对 DIC 的保护作用及其潜在机制。超声心动图、心肌细胞损伤生物标志物、血清肌酸激酶、肌酸激酶同工酶和乳酸脱氢酶以及组织学染色结果显示，岩藻依聚糖显着减轻 DIC 小鼠的心肌损伤并改善心功能。透射电子显微镜；脂质活性氧、谷胱甘肽和丙二醛的水平；铁死亡相关标记物；并测定心脏组织中谷胱甘肽过氧化物酶4（GPX4）、转铁蛋白受体蛋白1、铁蛋白重链1、血红素加氧酶1等调节因子，探讨岩藻依聚糖对Dox诱导的铁死亡的影响。这些结果表明岩藻依聚糖可以抑制Dox引起的心肌细胞铁死亡。体外实验表明，沉默心肌细胞中的核因子-红细胞2相关因子2（Nrf2）可降低岩藻依聚糖对铁死亡的抑制作用。因此，岩藻依聚糖具有通过 Nrf2/GPX4 途径抑制铁死亡来改善 DIC 的潜力。版权所有 © 2024。由 Elsevier B.V. 出版。

Doxorubicin (Dox), a chemotherapeutic agent frequently used to treat cancer, elicits cardiotoxicity, a condition referred to as Dox-induced cardiotoxicity (DIC), and ferroptosis plays a contributory role in its pathophysiology. Fucoidan, a polysaccharide with various biological activities and safety profile, has potential therapeutic and pharmaceutical applications. This study aimed to investigate the protective effects and underlying mechanisms of fucoidan in DIC. Echocardiography, biomarkers of cardiomyocyte injury, serum creatine kinase, creatine kinase isoenzyme and lactate dehydrogenase, as well as histological staining results, revealed that fucoidan significantly reduced myocardial damage and improved cardiac function in DIC mice. Transmission electron microscopy; levels of lipid reactive oxygen species, glutathione, and malondialdehyde; ferroptosis-related markers; and regulatory factors such as glutathione peroxidase 4 (GPX4), transferrin receptor protein-1, ferritin heavy chain-1, heme oxygenase-1 in the heart tissue were measured to explore the effect of fucoidan on Dox-induced ferroptosis. These results suggested that fucoidan could inhibit cardiomyocyte ferroptosis caused by Dox. In vitro experiments revealed that silencing nuclear factor-erythroid 2-related factor 2 (Nrf2) in cardiomyocytes reduced the inhibitory effect of fucoidan on ferroptosis. Hence, fucoidan has the potential to ameliorate DIC by inhibiting ferroptosis via the Nrf2/GPX4 pathway.Copyright © 2024. Published by Elsevier B.V.