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Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin‐induced myocardial injury

Zhang, Qingling, Zhang, Yunpeng, Xie, Bingxin, Liu, Daiqi, Wang, Yueying, Zhou, Zandong, Zhang, Yue, King, Emma, Tse, Gary, Liu, Tong and others. (2023) Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin‐induced myocardial injury. Cancer Innovation, 2 (4). pp. 253-264. ISSN 2770-9183. (doi:10.1002/cai2.64) (KAR id:100695)


Background: Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose‐dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin‐induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin‐induced myocardial injury. This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro.

Methods: Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group. Body weight, echocardiography, surface electrocardiogram, and myocardial histomorphology were measured. The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups (phosphate‐buffered saline, doxorubicin, and doxorubicin with resveratrol).

Results: Compared to the control group, the doxorubicin group showed a lower body weight and higher systolic arterial pressure, associated with reduced left ventricular ejection fraction and left ventricular fractional shortening, prolonged PR interval, and QT interval. These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes, increased protein expression levels of α‐smooth muscle actin and caspase 3, and reduced protein expression levels of Mitofusin2 (MFN2) and Sirtuin1 (SIRT1). Compared to the doxorubicin group, doxorubicin + resveratrol treatment reduced caspase 3 and manganese superoxide dismutase, and increased MFN2 and SIRT1 expression levels.

Conclusion: Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion. Resveratrol ameliorates doxorubicin‐induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.

Item Type: Article
DOI/Identification number: 10.1002/cai2.64
Uncontrolled keywords: cardio‐oncology, doxorubicin‐induced cardiomyopathy, mitochondria function, resveratrol, SIRT1 agonists
Subjects: R Medicine
Divisions: Divisions > Division of Natural Sciences > Kent and Medway Medical School
Funders: National Natural Science Foundation of China (
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 31 Mar 2023 14:13 UTC
Last Modified: 17 Nov 2023 14:53 UTC
Resource URI: (The current URI for this page, for reference purposes)

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