Mechanisms of Anthracycline-Induced Cardiotoxicity: Is Mitochondrial Dysfunction the Answer?

Abstract

Cardiac side effects are a major drawback of anticancer therapies, often requiring the use of low and less effective doses or even discontinuation of the drug. Among all the drugs known to cause severe cardiotoxicity are anthracyclines that, though being the oldest chemotherapeutic drugs, are still a mainstay in the treatment of solid and hematological tumors. The recent expansion of the field of Cardio-Oncology, a branch of cardiology dealing with prevention or treatment of heart complications due to cancer treatment, has greatly improved our knowledge of the molecular mechanisms behind anthracycline-induced cardiotoxicity (AIC). Despite excessive generation of reactive oxygen species was originally believed to be the main cause of AIC, recent evidence points to the involvement of a plethora of different mechanisms that, interestingly, mainly converge on deregulation of mitochondrial function. In this review, we will describe how anthracyclines affect cardiac mitochondria and how these organelles contribute to AIC. Furthermore, we will discuss how drugs specifically targeting mitochondrial dysfunction and/or mitochondria-targeted drugs could be therapeutically exploited to treat AIC.

Effects of Cardioprotective Tactics on the Myocardial Perfusion and Contractile Function of the Left Ventricular Myocardium in Cancer Patients with Evidence of Doxorubicin-Induced Cardiotoxicity

“…Однако в Российской Федерации в настоящее время препарат не зарегистрирован. Кроме того, хотя дексразоксан предотвращает антрациклин-индуцированную кардиотоксичность, его кардиопротективные эффекты не считаются достаточными, поскольку кардиотоксические механизмы антрациклинов многочисленны, а дексразоксан подавляет только некоторые из них [12][13][14][15].…”

Low Glucose Enhances the Cytoprotective Effect of Metformin Against Doxorubicin Induced Cytotoxicity in Normal Cells

“…Binding of doxorubicin to cardiolipin in the inner mitochondrial membrane can lead to mitochondrial dysfunction and can inactivate mitochondrial complexes I, III, IV, and V, phosphate carrier, and ATP-ADP translocase [25][26][27]. The spare respiratory capacity of mitochondria in response to oxidative stress and energetic insufficiency is important [28].…”

Mitochondrial Dysfunction and Heart Disease: Critical Appraisal of an Overlooked Association

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