Daidzein ameliorates doxorubicin-induced cardiac injury by inhibiting autophagy and apoptosis in rats

被引:0
|
作者
Wu, Jinxia [1 ]
Li, Kexue [1 ]
Liu, Yan [1 ]
Feng, Ailu [1 ]
Liu, Chunyang [1 ]
Adu-Amankwaah, Joseph [1 ]
Ji, Miaojin [2 ,3 ]
Ma, Yanhong [1 ]
Hao, Yanling [1 ]
Bu, Huimin [1 ]
Sun, Hong [1 ]
机构
[1] Xuzhou Med Univ, Dept Physiol, Xuzhou 221004, Jiangsu, Peoples R China
[2] Xuzhou Med Univ, Jiangsu Prov Key Lab Anesthesiol, Xuzhou 221004, Jiangsu, Peoples R China
[3] Xuzhou Med Univ, Sch Anesthesiol, Jiangsu Prov Key Lab Anesthesia & Analgesia Applic, Xuzhou 221004, Jiangsu, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
OXIDATIVE STRESS; CELL-DEATH; GENISTEIN; ACTIVATION; CANCER; AKT; CARDIOTOXICITY; CARDIOMYOPATHY; HYPERTROPHY; DYSFUNCTION;
D O I
10.1039/d2fo03416f
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Backgrounds: Doxorubicin (Dox) is a classical antitumor antibiotic widely restricted for use due to its cardiotoxicity. Daidzein (Daid) is a soy isoflavone that enhances antioxidant enzyme systems and inhibits apoptosis to prevent cardiovascular diseases. In this study, we intended to assess whether Daid protects against Dox-induced cardiotoxicity and explored its underlying mechanisms. Methods: Male Sprague-Dawley (SD) rats were divided into five groups: control (Ctrl), 40 mg per kg per day Daidzein (Daid), 3 mg per kg per week doxorubicin (Dox), 20 mg per kg per day Daidzein + 3 mg per kg per week doxorubicin (Daid20 + Dox) and 40 mg per kg per day Daidzein + 3 mg per kg per week doxorubicin (Daid40 + Dox) groups. Cardiac function assessments, immunohistochemistry (IHC) and immunofluorescence (IF) analyses were initially performed in each group of rats. Secondly, the cell proliferative capacity analysis, AO staining, and LC3 puncta analysis were employed to evaluate the cellular response to Dox in H9c2 cells. Ultimately, the protein expressions of cleaved caspase3, LC3 II, Bcl-2, Bax, Akt, p-Akt, and cyclin D1 were examined by western blotting. Results: Pretreatment with a low dose of Daid rather than a high dose significantly enhanced cardiac function and alleviated histopathological deterioration of cardiomyocytes induced by Dox. Daid downregulated the protein levels of Bax, LC3 II, cleaved caspase3 and p-Akt, while up-regulating Bcl-2 and cyclin D1. The Akt agonist SC79 could invalidate all the protective effects of Daid both in vivo and in vitro. Conclusions: Daid reduced autophagy and apoptosis by inhibiting the PI3K/Akt pathway, thereby protecting the hearts from Dox-induced cardiac damage.
引用
收藏
页码:934 / 945
页数:12
相关论文
共 50 条
  • [1] Protective role of cezanne in doxorubicin-induced cardiotoxicity by inhibiting autophagy, apoptosis and oxidative stress
    Zhang, Jiayan
    Zha, Yafang
    Jiao, Yuheng
    Li, Yanyan
    Zhang, Song
    TOXICOLOGY, 2023, 485
  • [2] Scutellarin Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Myocardial Fibrosis, Apoptosis and Autophagy in Rats
    Sun, Xipeng
    Zhou, Li
    Han, Yonglong
    Yang, Quanjun
    Li, Xingxia
    Xin, Bo
    Chi, Mengyi
    Wang, Yaxian
    Guo, Cheng
    CHEMISTRY & BIODIVERSITY, 2023, 20 (01)
  • [3] Tetrandrine Attenuated Doxorubicin-Induced Acute Cardiac Injury in Mice
    Li, Gang
    Li, Wen-Rui
    Jin, Ya-Ge
    Jie, Qi-Qiang
    Wang, Cheng-Yu
    Wu, Lin
    BIOMED RESEARCH INTERNATIONAL, 2020, 2020
  • [4] Allicin ameliorates doxorubicin-induced cardiotoxicity in rats via suppression of oxidative stress, inflammation and apoptosis
    Abdel-Daim, Mohamed M.
    Kilany, Omnia E.
    Khalifa, Hesham A.
    Ahmed, Amal A. M.
    CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2017, 80 (04) : 745 - 753
  • [5] Cardiotonic Activity of Daidzein Against Doxorubicin-Induced Congestive Cardiac Failure in Rats
    Li, Yuan
    Li, Zhanhu
    Liu, Shuai
    Su, Yakun
    Li, Yong
    CURRENT TOPICS IN NUTRACEUTICAL RESEARCH, 2022, 20 (01) : 106 - 112
  • [6] Evaluation of biomarkers for doxorubicin-induced cardiac injury in rats
    Pan, Dong-Sheng
    Li, Bo
    Wang, San-Long
    EXPERIMENTAL AND THERAPEUTIC MEDICINE, 2022, 24 (06)
  • [7] C1qTNF-related protein-6 protects against doxorubicin-induced cardiac injury
    Zheng, Wei-Feng
    Zhang, Shou-Yan
    Ma, Hui-Fang
    Chang, Xue-Wei
    Wang, Hao
    JOURNAL OF CELLULAR BIOCHEMISTRY, 2019, 120 (06) : 10748 - 10755
  • [8] Rutin attenuates doxorubicin-induced cardiotoxicity via regulating autophagy and apoptosis
    Ma, Yanyan
    Yang, Lifang
    Ma, Jipeng
    Lu, Linhe
    Wang, Xiaowu
    Ren, Jun
    Yang, Jian
    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2017, 1863 (08): : 1904 - 1911
  • [9] C1qTNF-related protein 1 attenuates doxorubicin-induced cardiac injury via activation of AKT
    Chen, Hongrui
    Gao, Lu
    Huang, Zhen
    Liu, Yuan
    Guo, Sen
    Xing, Junhui
    Meng, Zhe
    Liang, Cui
    Li, Yapeng
    Yao, Rui
    Li, Ling
    Zhang, Yanzhou
    Gu, Heping
    Liu, Yuzhou
    LIFE SCIENCES, 2018, 207 : 492 - 498
  • [10] Febuxostat ameliorates doxorubicin-induced cardiotoxicity in rats
    Krishnamurthy, Bhaskar
    Rani, Neha
    Bharti, Saurabh
    Golechha, Mahaveer
    Bhatia, Jagriti
    Nag, Tapas Chandra
    Ray, Ruma
    Arava, Sudheer
    Arya, Dharamvir Singh
    CHEMICO-BIOLOGICAL INTERACTIONS, 2015, 237 : 96 - 103