Chemotherapeutic agent induced cardiomyopathy

Doxorubicin (Dox) is a widely utilized chemotherapeutic agent in clinical oncology for treating various cancers. However, its clinical use is constrained by its significant side effects. Among these, the development of cardiomyopathy, characterized by cardiac remodeling and eventual heart failure, stands as a major concern following Dox chemotherapy.In our current investigation, we have showcased the efficacy of MLN4924 in mitigating doxorubicin-induced cardiotoxicity through direct inhibition of the NEDD8-activating enzyme, NAE...

Doxorubicin is an effective chemotherapeutic agent in the treatment of solid hematological and non-hematological carcinoma. However, its long-term usage could result in side effects, such as cardiomyopathy, chronic heart failure, neurotoxicity and cancer cell resistance. In this study, we reported the sensitivity enhancement of A549 human lung cancer cells on doxorubicin at a low dose (0.1 ppm) in combination with 10-60 ppm of crude and alkaloid extracts derived from the leaves of Kratom ( Mitragyna speciosa (Korth...

Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding...

Dose-limiting toxicities (DLTs) are severe adverse effects that define the maximum tolerated dose of a cancer drug. In addition to the specific mechanisms of each drug, common contributing factors include inflammation, apoptosis, ion imbalances, and tissue-specific enzyme deficiencies. Among various DLTs are bleomycin-induced pulmonary fibrosis, doxorubicin-induced cardiomyopathy, cisplatin-induced nephrotoxicity, methotrexate-induced hepatotoxicity, vincristine-induced neurotoxicity, paclitaxel-induced peripheral neuropathy, and irinotecan, which elicits severe diarrhea...

Doxorubicin, an anthracycline chemotherapeutic agent, elicits a deleterious cardiotoxicity known as doxorubicin-induced cardiomyopathy (DIC) that circumscribes its chemotherapy utility for malignancies. Recent empirical evidence implicates ferroptosis, an iron-dependent form of regulated cell death, as playing a pivotal role in the pathogenesis of DIC. We postulated that anti-ferroptosis agents may constitute a novel therapeutic strategy for mitigating DIC. To test this hypothesis, we engineered baicalin-peptide supramolecular self-assembled nanofibers designed to selectively target the angiotensin II type I receptor (AT1R), which is upregulated in doxorubicin-damaged cardiomyocytes...

With the progression of tumor treatment, the 5-year survival rate of breast cancer is close to 90%. Cardiovascular toxicity caused by chemotherapy has become a vital factor affecting the survival of patients with breast cancer. Anthracyclines, such as doxorubicin, are still some of the most effective chemotherapeutic agents, but their resulting cardiotoxicity is generally considered to be progressive and irreversible. In addition to anthracyclines, platinum- and alkyl-based antitumor drugs also demonstrate certain cardiotoxic effects...

BACKGROUND: Left ventricular dysfunction and cardiomyopathy are well documented adverse effects associated with chemotherapy agents. Limited information exists regarding the impact of chemotherapeutic agents on the integrity and function of the right ventricle (RV). OBJECTIVES: The current metanalysis compared pre- chemotherapy versus post- chemotherapy RV parameters measured on 2D echocardiography in patients receiving anthracycline and/or trastuzumab across all breast cancer patients...

Anthracyclines, such as doxorubicin (Dox), are widely used chemotherapeutic agents for the treatment of solid tumors and hematologic malignancies. However, they frequently induce cardiotoxicity leading to dilated cardiomyopathy and heart failure. This study sought to investigate the role of the Exchange Protein directly Activated by cAMP (EPAC) in Dox-induced cardiotoxicity and the potential cardioprotective effects of EPAC inhibition. We show that Dox induces DNA damage and cardiomyocyte cell death with apoptotic features...

Chemotherapeutic agents, such as doxorubicin (DOX), may cause cardiomyopathy, even life-threatening arrhythmias in cancer patients. Ferroptosis-an iron-dependent oxidative form of programmed necrosis, plays a pivotal role in DOX-induced cardiomyopathy (DIC). Prostaglandins (PGs) are bioactive signaling molecules that profoundly modulate cardiac performance in both physiologic and pathologic conditions. Here, we found that PGE2 production and its E-prostanoid 1 receptor (EP1) expression were upregulated in erastin (a ferroptosis inducer) or DOX-treated cardiomyocytes...

Trastuzumab (TRZ) is a first-line chemotherapeutic agent for HER-2 (ErbB2)-positive breast cancer. Unfortunately, its clinical use is limited due to its cardiotoxicity, referred to as TRZ-induced cardiotoxicity (TIC). However, the exact molecular mechanisms underlying the development of TIC remain unclear. Iron and lipid metabolism and redox reactions participate in the development of ferroptosis. Here, we show that ferroptosis-mediated mitochondrial dysfunction is involved in TIC in vivo and in vitro. We first established TIC models with BALB/c mice or neonatal rat cardiomyocytes and confirmed cardiomyopathy with echocardiography and inhibition of cell viability with a cell counting kit-8 examination, respectively...

Doxorubicin (DOX) as a chemotherapeutic agent can cause mitochondrial dysfunction and heart failure. COX5A has been described as an important regulator of mitochondrial energy metabolism. We investigate the roles of COX5A in DOX-induced cardiomyopathy and explore the underlying mechanisms. C57BL/6J mice and H9c2 cardiomyoblasts were treated with DOX, and the COX5A expression was assessed. An adeno-associated virus serum type 9 (AAV9) and lenti-virus system were used to upregulate COX5A expression. Echocardiographic parameters, morphological and histological analyses, transmission electron microscope and immunofluorescence assays were used to assess cardiac and mitochondrial function...

Cancer is one of the leading causes of morbidity and mortality in the pediatric population with the most common cancer being acute lymphoblastic leukemia. One of the most common drugs used in the treatment is the anthracycline group of chemotherapeutic agents, and a major side effect is cardiotoxicity. Dexrazoxane, a member of the cardioprotective agents' group of medications, is the only current FDA-approved medication to tackle cardiotoxicity. The mechanism of action in which dexrazoxane is cardioprotective is by halting necroptosis in cardiomyocytes after anthracycline therapy and concurrently binds with iron and reduces the formation of anthracycline-iron complexes and reactive oxygen species...

Adriamycin is a well-known anthracycline chemotherapeutic agent widely used in treating a variety of malignancies. However, Adriamycin's clinical use is limited due to its adverse side-effects, most importantly cardiomyopathy. Adriamycin-induced cardiotoxicity reportedly includes mitochondrial dysfunction. We hypothesize that modulation of KLF4, a key regulator of cardiac mitochondrial homeostasis might play a role in the development of Adriamycin-induced cardiomyopathy. Therefore, in the current work, we evaluated the interaction of Adriamycin with KLF4 and its subsequent downstream targets...

Nanotechnology has emerged as a promising approach for the targeted delivery of therapeutic agents while improving their efficacy and safety. As a result, nanomaterial development for the selective targeting of cancers, with the possibility of treating off-target, detrimental sequelae caused by chemotherapy, is an important area of research. Breast and ovarian cancer are among the most common cancer types in women, and chemotherapy is an essential treatment modality for these diseases. However, chemotherapy-induced neurotoxicity, neuropathy, and cardiomyopathy are common side effects that can affect breast and ovarian cancer survivors quality of life...

Doxorubicin (DOX), a broad-spectrum chemotherapeutic agent for various cancers, has limited clinical application because of its serious cardiotoxicity, which is due to different mechanisms, including cardiac ferroptosis and oxidative stress. Some drugs, such as berberine or dioscin, show efficacy in impeding DOX-induced cardiotoxicity by activating Sirtuin 1 (Sirt1). However, there is no direct evidence to clarify the role of Sirt1 in DOX-induced cardiomyopathy and its underlying role in cardiac ferroptosis...

Homeostatic regulation of cardiomyocytes plays a critical role in maintaining normal physiological activity of cardiac tissue. Severe cardiotoxicity can lead to heart disease, including but not limited to arrhythmias, myocardial infarction and cardiac hypertrophy. In recent years, significant progress has been made in developing new therapies for cancer that have dramatically changed the treatment of several malignancies and continue to improve patient survival, but can also lead to serious cardiac adverse effects...

Doxorubicin (DOX) is a chemotherapeutic agent that can cause cardiotoxicity leading to progressive, chronic, life-threatening cardiomyopathy, called DOX-induced cardiomyopathy (DIC). DIC is a fatal cardiomyopathy with a worse prognosis compared to other cardiomyopathies and limits the use of DOX in malignancies due to its cardiotoxicity. DIC has been proven to be associated with reactive oxygen species (ROS)-induced side effect damage in cardiac myocytes. Currently, scavenging of reactive oxygen species is a practical strategy to reduce chemotherapy-associated DIC...

Antiblastic drugs-induced cardiomyopathy remains a relevant cause of morbidity and mortality, during and after chemotherapy, despite the progression in protective therapy against cardiovascular diseases and myocardial function. In the last few decades, many groups of researchers have focused their attention on studying the metabolic profile, first in animals, and, subsequently, in humans, looking for profiles which could be able to predict drug-induced cardiotoxicity and cardiovascular damage. In clinical practice, patients identified as being at risk of developing cardiotoxicity undergo a close follow-up and more tailored therapies...

PURPOSE: Doxorubicin is an important cancer chemotherapeutic agent with severe cardiotoxic effects that eventually lead to dilated cardiomyopathy (DCM). Calsyntenin-1(CLSTN1) plays a critical role in the nervous system, but its relevance in cardiovascular diseases is unknown. We investigated the significance of CLSTN1 in doxorubicin-induced DCM. METHODS: CLSTN1 expression in doxorubicin-induced DCM rats and H9c2 cells was determined using western blotting. To further explore the functions of CLSTN1, a cardiac-specific CLSTN1 overexpression rat model was constructed...

PURPOSE OF REVIEW: This study is aimed at reviewing the recent progress in Drp1 inhibition as a novel approach for reducing doxorubicin-induced cardiotoxicity and for improving cancer treatment. RECENT FINDINGS: Anthracyclines (e.g. doxorubicin) are one of the most common and effective chemotherapeutic agents to treat a variety of cancers. However, the clinical usage of doxorubicin has been hampered by its severe cardiotoxic side effects leading to heart failure...