褐藻糖胶
心脏毒性
阿霉素
GPX4
化学
癌症研究
药理学
医学
毒性
化疗
氧化应激
生物化学
内科学
多糖
过氧化氢酶
有机化学
谷胱甘肽过氧化物酶
作者
Yizhi Wang,Jiawen Han,Shifang Zhan,Chenyu Guo,Shuangneng Yin,Lin Zhan,Qianyi Zhou,Ruiying Liu,Hua Yan,Xiaoyan Wang,Dan Yan
标识
DOI:10.1016/j.ijbiomac.2024.133792
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI