Acylated Ghrelin Protects the Hearts of Rats from Doxorubicin-Induced Fas/FasL Apoptosis by Stimulating SERCA2a Mediated by Activation of PKA and Akt

Shati, Ali A.; Dallak, Mohammad

doi:10.1007/s12012-019-09527-8

Cited by 6 publications

(5 citation statements)

References 76 publications

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“…SERCA2a plays a vital role in restoring the excessive amount of Ca 2+ in the cytosol, the uncontrolled level of Ca 2+ in cells causes the impairment of contractile cardiac muscles [68]. Furthermore, doxorubicin also inhibits the Na + /Ca 2+ exchanger [69], and the increase in doxorubicin levels also causes an increase in the expression of the ryanodine receptor channels, which leads to the massive release of Ca 2+ [70,71]. Interestingly, SERCA is inhibited by the ROS-mediated S-oxidation of the conserved Cys 674 along with increasing RyR2 [72].…”

Section: Calcium Homeostasis Dysregulationmentioning

confidence: 99%

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

et al. 2022

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Doxorubicin is a widely used and promising anticancer drug; however, a severe dose-dependent cardiotoxicity hampers its therapeutic value. Doxorubicin may cause acute and chronic issues, depending on the duration of toxicity. In clinical practice, the accumulative toxic dose is up to 400 mg/m2 and increasing the dose will increase the probability of cardiac toxicity. Several molecular mechanisms underlying the pathogenesis of doxorubicin cardiotoxicity have been proposed, including oxidative stress, topoisomerase beta II inhibition, mitochondrial dysfunction, Ca2+ homeostasis dysregulation, intracellular iron accumulation, ensuing cell death (apoptosis and necrosis), autophagy, and myofibrillar disarray and loss. Natural products including flavonoids have been widely studied both in cell, animal, and human models which proves that flavonoids alleviate cardiac toxicity caused by doxorubicin. This review comprehensively summarizes cardioprotective activity flavonoids including quercetin, luteolin, rutin, apigenin, naringenin, and hesperidin against doxorubicin, both in in vitro and in vivo models.

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Section: Calcium Homeostasis Dysregulationmentioning

confidence: 99%

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

et al. 2022

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“…Several recent studies by two independent research groups A. Shati et al and M. Kihara et al demonstrated pronounced anti-apoptotic and antifibrotic effects of the acylated form of ghrelin [104][105][106]. Thus, recent studies indicate that ghrelin and its acylated form are promising cardioprotective drugs for the management of patients with signs of doxorubicin-induced cardiotoxicity.…”

Section: Mtorc1 Mammalian Target Of Rapamycin Complex 1; Ros Reactive...mentioning

confidence: 99%

The Essential Strategies to Mitigate Cardiotoxicity Caused by Doxorubicin

Chaulin

2023

Life

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The study of mechanisms underlying cardiotoxicity of doxorubicin and the development of strategies to mitigate doxorubicin-induced cardiotoxicity are the most relevant issues of modern cardio-oncology. This is due to the high prevalence of cancer in the population and the need for frequent use of highly effective chemotherapeutic agents, in particular anthracyclines, for optimal management of cancer patients. However, while being a potent agent to counteract cancer, doxorubicin also affects the cardiovascular systems of patients undergoing chemotherapy in a significant and unfavorable fashion. Consecutively reviewed in this article are risk factors and mechanisms of doxorubicin cardiotoxicity, and the essential strategies to mitigate cardiotoxic effects of doxorubicin treatment in cancer patients are discussed.

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“…Interestingly, Eid and colleagues have shown that acylated ghrelin has cardioprotective effects via the activation of STAT3 and inhibition of STAT1 in rats, and this process is mediated by the receptor GHSR1a and activation of JAK2 [ 36 , 37 ]. Acylated ghrelin also inhibits NFAT-4 nuclear translocation to downregulate Fas and FasL, upregulate SERCA2a, and increase the activity of PKA and Akt, resulting in the inhibition of extrinsic cell death and restoration of normal Ca homeostasis [ 38 ] ( Fig. 1 ).…”

Section: Mechanism and Function Of Acetylation In Cardiotoxicitymentioning

confidence: 99%

Role of acetylation in doxorubicin-induced cardiotoxicity

Yang

Wang

et al. 2021

Redox Biology

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As a potent chemotherapeutic agent, doxorubicin (DOX) is widely used for the treatment of a variety of cancers However, its clinical utility is limited by dose-dependent cardiotoxicity, and pathogenesis has traditionally been attributed to the formation of reactive oxygen species (ROS). Accordingly, the prevention of DOX-induced cardiotoxicity is an indispensable goal to optimize therapeutic regimens and reduce morbidity. Acetylation is an emerging and important epigenetic modification regulated by histone deacetylases (HDACs) and histone acetyltransferases (HATs). Despite extensive studies of the molecular basis and biological functions of acetylation, the application of acetylation as a therapeutic target for cardiotoxicity is in the initial stage, and further studies are required to clarify the complex acetylation network and improve the clinical management of cardiotoxicity. In this review, we summarize the pivotal functions of HDACs and HATs in DOX-induced oxidative stress, the underlying mechanisms, the contributions of noncoding RNAs (ncRNAs) and exercise-mediated deacetylases to cardiotoxicity. Furthermore, we describe research progress related to several important SIRT activators and HDAC inhibitors with potential clinical value for chemotherapy and cardiotoxicity. Collectively, a comprehensive understanding of specific roles and recent developments of acetylation in doxorubicin-induced cardiotoxicity will provide a basis for improved treatment outcomes in cancer and cardiovascular diseases.

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Acylated Ghrelin Protects the Hearts of Rats from Doxorubicin-Induced Fas/FasL Apoptosis by Stimulating SERCA2a Mediated by Activation of PKA and Akt

Cited by 6 publications

References 76 publications

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

The Role of Flavonoids as a Cardioprotective Strategy against Doxorubicin-Induced Cardiotoxicity: A Review

The Essential Strategies to Mitigate Cardiotoxicity Caused by Doxorubicin

Role of acetylation in doxorubicin-induced cardiotoxicity

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