Dexrazoxane ameliorates doxorubicin-induced cardiotoxicity by inhibiting both apoptosis and necroptosis in cardiomyocytes

Yu, Xiaoxue; Ruan, Yuanyuan; Huang, Xiuqing; Dou, Lin; Lan, Ming; Chen, Ju; Chen, Beidong; Gong, Huan; Wang, Que; Yan, Mingjing; Sun, Shenghui; Qiu, Quan; Zhang, Xiyue; Man, Yong; Tang, Weiqing; Li, Jian; Shen, Tao

doi:10.1016/j.bbrc.2019.12.027

Cited by 67 publications

(44 citation statements)

References 33 publications

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“…It has been demonstrated that RIPK3 is activated by DOX to bind with phosphorylated-CaMKII, causing the opening of mitochondrial permeability transition pore (MTPT), and resulting in necroptosis (Zhang T. et al, 2016). More importantly, dexrazoxane alleviated Dox-induced inflammation and cardiomyocyte necroptosis through inhibiting p38-MAPK/nuclear factor kappa-B (NF-κB) signal (Yu et al, 2020).…”

Section: Necroptosismentioning

confidence: 99%

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Wei

Zhang

et al. 2020

Front. Cell Dev. Biol.

101

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Homeostatic regulation of cardiomyocytes plays a crucial role in maintaining the normal physiological activity of cardiac tissue. Severe cardiotoxicity results in cardiac diseases including but not limited to arrhythmia, myocardial infarction and myocardial hypertrophy. Drug-induced cardiotoxicity limits or forbids further use of the implicated drugs. Such drugs that are currently available in the clinic include anti-tumor drugs (doxorubicin, cisplatin, trastuzumab, etc.), antidiabetic drugs (rosiglitazone and pioglitazone), and an antiviral drug (zidovudine). This review focused on cardiomyocyte death forms and related mechanisms underlying clinical drug-induced cardiotoxicity, including apoptosis, autophagy, necrosis, necroptosis, pryoptosis, and ferroptosis. The key proteins involved in cardiomyocyte death signaling were discussed and evaluated, aiming to provide a theoretical basis and target for the prevention and treatment of drug-induced cardiotoxicity in the clinical practice.

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Section: Necroptosismentioning

confidence: 99%

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Wei

Zhang

et al. 2020

Front. Cell Dev. Biol.

101

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“…Furthermore, apoptotic proteins such as Bax and caspase-3 undergo downregulation, while antiapoptotic factor Bcl-2 demonstrates an increase in expression to ameliorate DOX side effects [98]. Taking everything into together, studies demonstrate that inflammation, oxidative stress and apoptosis are induced following DOX exposure in normal cells and protective agents possess regulatory effect on aforementioned mechanisms in reducing adverse effects of DOX [99][100][101][102]. Figure 1 demonstrates the chemical structure of curcumin and doxorubicin.…”

Section: Doxorubicin: Cancer Resistance and Side Effectsmentioning

confidence: 99%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

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“…Cultured cardiomyocytes represent an excellent model system to study various aspects of cardiomyocyte physiology, as they closely mimic many in vivo properties of cardiomyocytes (Louch et al., 2011). Neonatal murine cardiomyocyte cultures can be used for in vitro studies on bioenergetics (Tachibana et al., 2019), electrophysiology (Nuss & Marban, 1994), myofibrillogenesis (Liu et al., 2013; White et al., 2018), cell death (Fu et al., 2004), and mechanisms of drug‐induced cardiotoxicity (Meng et al., 2019; Yu et al., 2020), and can serve as a model for hypoxia (Long et al., 1997; Tanaka et al., 1994) and hypertrophy (Miyata & Haneda, 1994; Ravi et al., 2018; Sarikhani et al., 2018). Other practical applications of neonatal murine cardiomyocytes are discussed below, in Understanding Results.…”

Section: Commentarymentioning

confidence: 99%

Isolation and Culture of Neonatal Murine Primary Cardiomyocytes

et al. 2021

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The cardiomyocyte is the main cell type in the heart responsible for its contractile function. Culturing primary cardiomyocytes from mammalian sources to study their function remains challenging as they are terminally differentiated and cease to multiply soon after birth. The major technical hurdles associated with primary cardiomyocyte culture include attaining high yields, obtaining healthy/viable cells that show spontaneous contractions upon culture, and avoiding contamination by non-myocyte cardiac cell types such as fibroblasts and endothelial cells. The yield and the quality of the cardiomyocytes obtained are impacted by a variety of factors, such as the purity of the reagents, composition of the digestion mixture, the digestion conditions, and the temperature of the tissue during different steps of isolation. Here, we provide a simplified workflow to isolate, culture, and maintain neonatal primary cardiomyocytes from rats/mice in culture dishes, which can then be used to study, for instance, cardiac hypertrophy and drug-induced cardiotoxicity.

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Dexrazoxane ameliorates doxorubicin-induced cardiotoxicity by inhibiting both apoptosis and necroptosis in cardiomyocytes

Cited by 67 publications

References 33 publications

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Isolation and Culture of Neonatal Murine Primary Cardiomyocytes

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