Doxorubicin induced cardio toxicity through sirtuins mediated mitochondrial disruption

Ahmad, Nisar; Ullah, Arfan; Chu, Peng; Tian, Wenzhang; Tang, Zeyao; Sun, Zhaolin

doi:10.1016/j.cbi.2022.110028

Cited by 11 publications

(5 citation statements)

References 149 publications

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“…Mammalian cardiomyocytes almost completely lose their ability to proliferate in adulthood, and will be replaced by scar tissue after cardiomyocyte death, resulting in myocardial structural and electrophysiological dysfunction, eventually develop into cardiac remodeling [ 38 , 39 ]. Previous studies have shown that Dox can mediate mitochondrial dysfunction and aggravate oxidative stress injury and cardiomyocyte apoptosis [ 40 ]. SLP-2, as a mitochondrial inner membrane protein, is closely related to oxidative stress [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Stomatin-like protein 2 deficiency exacerbates adverse cardiac remodeling

Jiang

et al. 2023

Cell Death Discov.

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Myocardial fibrosis, oxidative stress, and autophagy both play key roles in the progression of adverse cardiac remodeling. Stomatin-like protein 2 (SLP-2) is closely related to mitochondrial function, but little is known about its role and mechanism in cardiac remodeling. We developed doxorubicin (Dox), angiotensin (Ang) II, and myocardial ischemia-reperfusion (I/R) injury induced cardiac remodeling model and Dox treated H9C2 cell injury model using SLP-2 knockout (SLP-2-/-) mice and H9C2 cells with low SLP-2 expression. We first examined cardiac functional and structural changes as well as levels of oxidative stress, apoptosis and autophagy. We found that SLP-2 deficiency leads to decreased cardiac function and promotes myocardial fibrosis. After Dox and Ang II treatment, SLP-2 deficiency further aggravated myocardial fibrosis, increased myocardial oxidative stress and apoptosis, and activated autophagy by inhibiting PI3K-Akt-mTOR signaling pathway, ultimately exacerbating adverse cardiac remodeling. Similarly, SLP-2 deficiency further exacerbates adverse cardiac remodeling after myocardial I/R injury. Moreover, we extracted cardiomyocyte mitochondria for proteomic analysis, suggesting that SLP-2 deficiency may be involved in myocardial I/R injury induced adverse cardiac remodeling by influencing ubiquitination of intramitochondrial proteins. In addition, the oxidative stress, apoptosis and autophagy levels of H9C2 cells with low SLP-2 expression were further enhanced, and the PI3K-Akt-mTOR signaling pathway was further inhibited under Dox stimulation. Our results suggest that SLP-2 deficiency promotes myocardial fibrosis, disrupts normal mitochondrial function, overactivates autophagy via PI3K-Akt-mTOR signaling pathway, affects the level of ubiquitination, leads to irreversible myocardial damage, and ultimately exacerbates adverse cardiac remodeling.

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Section: Discussionmentioning

confidence: 99%

Stomatin-like protein 2 deficiency exacerbates adverse cardiac remodeling

Jiang

et al. 2023

Cell Death Discov.

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“…Studies have shown that DOX induces chronic heart failure beyond its cumulative dose (700 mg/m in adults and 300 mg/m in children) ( Xu et al, 2020 ). Approximately 30 percent of patients develop acute cardiotoxicity following DOX administration, with ST-segment changes, tachycardia, and premature ventricular beats ( Ahmad et al, 2022 ). Most of the symptoms of acute cardiotoxicity can be reversed, and once acute cardiotoxicity persists, it will induce chronic toxicity to the heart.…”

Section: Cardiotoxicity Of First-line Chemotherapy Drugs For Osteosar...mentioning

confidence: 99%

Engineered biomaterial delivery strategies are used to reduce cardiotoxicity in osteosarcoma

Hou,

Wang,

Wang

2023

Front. Pharmacol.

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Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Chemotherapy drugs play an integral role in OS treatment. Preoperative neoadjuvant chemotherapy and postoperative conventional adjuvant chemotherapy improve survival in patients with OS. However, the toxic side effects of chemotherapy drugs are unavoidable. Cardiotoxicity is one of the common side effects of chemotherapy drugs that cannot be ignored. Chemotherapy drugs affect the destruction of mitochondrial autophagy and mitochondria-associated proteins to cause a decrease in cardiac ejection fraction and cardiomyocyte necrosis, which in turn causes heart failure and irreversible cardiomyopathy. Biomaterials play an important role in nanomedicine. Biomaterials act as carriers to deliver chemotherapy drugs precisely around tumor cells and continuously release carriers around the tumor. It not only promotes anti-tumor effects but also reduces the cardiotoxicity of chemotherapy drugs. In this paper, we first introduce the mechanism by which chemotherapy drugs commonly used in OS cause cardiotoxicity. Subsequently, we introduce biomaterials for reducing cardiotoxicity in OS chemotherapy. Finally, we prospect biomaterial delivery strategies to reduce cardiotoxicity in OS.

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“…Excessive formation of reactive oxygen species (ROS) during abnormal myocardial metabolism can also lead to cell membrane disruption. 13 Ischemic preconditioning (IP) and ischemic postconditioning are well-known protective strategies to reduce the size of the infarct. Research evidence suggests that all regulative strategies to protect myocardium and reduce infarct size are effective only when used in combination with eventual reperfusion, and that strategies to reduce IRI are critical.…”

Section: The Pathophysiological Mechanisms Of Ischemia-reperfusionmentioning

confidence: 99%

“…Excessive formation of reactive oxygen species (ROS) during abnormal myocardial metabolism can also lead to cell membrane disruption. 13…”

Section: Coronary Heart Diseasementioning

confidence: 99%

Myocardial protection by desflurane: from basic mechanisms to clinical applications

Han

Jun

2023

Journal of Cardiovascular Pharmacology

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Coronary heart disease (CHD) is an affliction that is common and has an adverse effect on patients' quality of life and survival while also raising the risk of intraoperative anesthesia. Mitochondria are the organelles most closely associated with the pathogenesis, development and prognosis of CHD. Ion abnormalities, an acidic environment, the production of reactive oxygen species, and other changes during abnormal myocardial metabolism cause the opening of mitochondrial permeability transition pores, which disrupts electron transport, impairs mitochondrial function, and even causes cell death. Differences in reliability and cost-effectiveness between desflurane and other volatile anesthetics are minor, but desflurane has shown better myocardial protective benefits in the surgical management of patients with coronary artery disease. The results of myocardial protection by desflurane are briefly summarized in this review, and biological functions of the mitochondrial permeability transition pore, mitochondrial electron transport chain, reactive oxygen species, atp-dependent potassium channels, G protein-coupled receptors, and protein kinase C are discussed in relation to the protective mechanism of desflurane. This article also discusses the effects of desflurane on patient hemodynamics, myocardial function, and postoperative parameters during coronary artery bypass grafting. Although there are limited and insufficient clinical investigations, they do highlight the possible advantages of desflurane and offer additional suggestions for patients.

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Doxorubicin induced cardio toxicity through sirtuins mediated mitochondrial disruption

Cited by 11 publications

References 149 publications

Stomatin-like protein 2 deficiency exacerbates adverse cardiac remodeling

Stomatin-like protein 2 deficiency exacerbates adverse cardiac remodeling

Engineered biomaterial delivery strategies are used to reduce cardiotoxicity in osteosarcoma

Myocardial protection by desflurane: from basic mechanisms to clinical applications

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