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  3. Fucoidan alleviates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via Nrf2/GPX4 pathway

Fucoidan alleviates doxorubicin-induced cardiotoxicity by inhibiting ferroptosis via Nrf2/GPX4 pathway

  • Int J Biol Macromol. 2024 Jul 9;276(Pt 1):133792. doi: 10.1016/j.ijbiomac.2024.133792.
Yizhi Wang 1,  Jiawen Han 1,  Shifang Zhan 1,  Chenyu Guo 1,  Shuangneng Yin 1,  Lin Zhan 1,  Qianyi Zhou 1,  Ruiying Liu 1,  Hua Yan 2,  Xiaoyan Wang 3,  Dan Yan 4
Affiliations

Affiliations

  • 1 Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, Hubei, China.
  • 2 Department of Cardiology, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan 430022, Hubei, China.
  • 3 Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Key Laboratory of Emergency and Trauma, Ministry of Education, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, Hainan, China. Electronic address: xiaoyanwang@hust.edu.cn.
  • 4 Institute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, Hubei, China; Department of Cardiology, Wuhan Asia Heart Hospital, Wuhan University of Science and Technology, Wuhan 430022, Hubei, China; Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, Hubei, China. Electronic address: Yandan@wust.edu.cn.
PMID: 38992539 DOI: 10.1016/j.ijbiomac.2024.133792
Abstract

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.

Keywords

Doxorubicin-induced cardiotoxicity; Ferroptosis; Fucoidan.

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