Результаты поиска

Integrated network toxicology and molecular docking strategy elucidate ferroptosis mechanisms underlying acetyl tributyl citrate induced cardiotoxicity.

This study aims to elucidate the cardiotoxic effects of acetyl tributyl citrate (ATBC) and unravel the underlying mechanisms governing the impact of this environmental pollutant on cardiac-related pathological processes. Ferroptosis is emerging as a critical cell death pathway, playing a pivotal role in adverse outcomes associated with exposure to environmental pollutants and toxins. Utilizing ChEMBL, STITCH, GeneCards, and OMIM databases, we first identified a comprehensive list of 269 potential targets closely linked to ATBC and cardiotoxicity. From the FerrDb v2 and GeneCards databases, we …

Cardiac reprogramming via transient overexpression of P-glycoprotein alleviates doxorubicin-induced cardiotoxicity in mice and pigs.

Doxorubicin-induced cardiotoxicity represents a significant clinical adverse effect associated with cancer chemotherapy treatment. Inspired by cancer drug resistance mechanisms, we propose a novel strategy termed transient overexpression of p-glycoprotein for cardiac reprogramming to induce cardiac drug resistance as a treatment for cardiotoxicity. This approach involves reprogramming cardiomyocytes by delivering lipid nanoparticles-based mRNA therapeutics to induce temporary p-glycoprotein overexpression, which in turn reduces intracellular doxorubicin levels and suppresses cytotoxic effects.…

Doxorubicin-induced early-onset chronic progressive cardiotoxicity, pharmacogenetics and survival among breast cancer patients in Zimbabwe.

BACKGROUND: Early-onset chronic progressive cardiotoxicity (ECPC) is a significant cause of morbidity and mortality among patients who receive doxorubicin-based chemotherapy for breast cancer. OBJECTIVE: To establish incidence of ECPC in black Zimbabwean women with breast cancer treated with doxorubicin and the resultant survival, and to describe the pharmacogenomic biomarkers' association with prognosis. METHOD: A prospective observational study was conducted in Zimbabwe with 50 participants who received doxorubicin-based treatment and were actively followed up to 12 months, with 3-monthly …

Immune Pathways in Doxorubicin Cardiotoxicity: A Cardio-Immunology Perspective: JACC CardioOncology State-of-the-Art Review.

Anthracyclines such as doxorubicin remain central to cancer therapy, but their clinical utility is constrained by dose-limiting cardiotoxicity and long-term cardiovascular sequelae. Although traditionally attributed to cardiomyocyte-intrinsic mechanisms, including mitochondrial dysfunction, oxidative stress, and DNA damage, emerging evidence demonstrates that these initial injuries rapidly activate the immune system, transforming doxorubicin-induced cardiotoxicity (DIC) into a multicellular inflammatory process. Release of mitochondrial and nuclear danger signals triggers innate immune pathway…

Three-dimensional quantification of ethanol-induced pericardial edema in zebrafish: A structural endpoint for cardiotoxicity assessment.

Ethanol-induced pericardial edema is a common morphological manifestation of developmental cardiotoxicity in zebrafish. However, there is currently a lack of methods that can provide objective and reproducible quantitative measurements of pericardial edema severity. Here, we established a non-invasive, three-dimensional (3D) quantitative framework using Spectral Domain Optical Coherence Tomography (SD-OCT) to resolve this limitation. Validation using a lipid-filled scattering phantom yielded measured and theoretical values with a relative error below 1%. No significant difference existed betwe…

Polystyrene nanoplastics induce cardiotoxicity by driving myocardial metabolic reprogramming via the SDHA/Succinate/HIF-1α axis.

Micro- and nano-plastics (MNPs) have emerged as ubiquitous environmental contaminants and are increasingly implicated in adverse cardiovascular outcomes, yet their induced cardiotoxicity and potential mechanisms remain poorly understood. This study integrated in vivo mouse models, AC16 cardiomyocytes and a human cardiac organoid-on-a-chip (COoC) platform to multi-dimensionally evaluate polystyrene nanoparticles (PS-NPs)-induced cardiac injury and clarify its key molecular mechanisms. We found that PS-NPs exposure induced pronounced structural and functional cardiac injury in mice and caused im…

Associations between CT-Based Body Composition and Cardiotoxicity and Overall Survival in Patients with Prostate Cancer.

RATIONALE AND OBJECTIVES: The purpose of this study was to investigate the associations of parameters of computed tomography (CT)-based body … CONCLUSION: Utilization of the CT-based SM index contributes to the baseline risk stratification of cardiotoxicity and OS in patients with prostate cancer treated with ADT.

Кардиотоксичность, вызванная множественными миэломатерапиями: механистическая конвергенция между протеиновыми ингибиторами, CAR-T и биконкретными антителами.

Сердечно-сосудистая токсичность стала важным препятствием на пути реализации полного клинического потенциала современной терапии для множественных миэломы (ММ), включая протеазонные ингибиторы (ИП), химерика антигенного рецептора Т-клеток (CAR-T) и CD3-engaging Биотипные антитела. Здесь мы обсуждаем эпидемиологию, лежащую в основе механистических путей, и новые стратегии предотвращения кардиотоксичности, вызванной терапией, в MM. На основе данных, полученных в ходе исследований по изучению мультиомики, доклинических моделей и данных наблюдений в реальном мире, мы синтезируем вклад митохондриал

Совпадение в аннотации оригинала
Cardiovascular toxicity has emerged as an important obstacle to realizing the complete clinical potential of contemporary therapies for mult … idemiology, underlying mechanistic pathways, and emerging strategies for preventing therapy-induced cardiotoxicity in MM. Based on evidence from multi-omics studies, preclinical models, and real-world observational data, we synthesize the contributions of mitochondrial dysfunction, unfolded protein response (UPR), endothelial injury, and systemic inflammation in …

Clozapine-associated cardiotoxicity: Risk factors and long-term cardiovascular outcomes from a multicentre propensity-matched analysis.

BACKGROUND: Clozapine-associated cardiotoxicity, including myocarditis, is a recognized early complication. Risk factors and long-term cardiovascular consequences remain poorly defined. AIM: To evaluate heart failure, arrhythmia, cardiomyopathy and mortality outcomes among clozapine-treated patients with and without cardiotoxicity. METHODS: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults exposed to clozapine were identified. Adults initiating clozapine were identified and classified by early cardiotoxicity, defined as elevated troponin within …

Polyphenol-rich Cucurbita formulation mitigates doxorubicin-induced cardiotoxicity in rats: biochemical, histological, and molecular docking insights.

Cardiovascular diseases (CVDs) remained a dominant cause of global mortality, driven in part by oxidative stress and inflammation. Current study set out to evaluate the antioxidant and cardioprotective effects of a polyphenol-rich formulation (PRCF) derived from Cucurbita pepo, Cucurbita moschata, and Cucurbita maxima in 1:1:1 ratio of the formulation. Animals were assembled into five groups: normal control, Doxorubicin-induced cardiotoxicity (DIC, 15 mg/kg intraperitoneal on day 14), positive control (quercetin 10 mg/kg/day orally for the period of 21 days), PRCF-250 and PRCF-500 (polyphenol-…

Evaluation of Cardiotoxicity in Lymphoproliferative Patients Treated With Anthracycline and Bruton's Tyrosine Kinase Inhibitor-Based Regimens.

BACKGROUND: The treatment of lymphoproliferative disorders has often included a range of cardiotoxic chemotherapy-focused regimens, in particular Bruton's tyrosine kinase inhibitors (BTKi) and anthracyclines. Despite these agents being commonly used in clinical practice, the specific process of cardiotoxicity and the prevention of the subsequent cardiac-based pathologies, including atrial fibrillation and hypertension, are increasing points of research. Many hematology-oncology tertiary centers incorporate these agents into regular treatment regimens for patients. A retrospective study from a …

Immunotherapy-Induced Cardiotoxicity: A Narrative Review of Real-World Case Reports, Recent Information and Clinical Evidence.

Immunotherapy is revolutionizing the treatment of cancer and other conditions. However, it also precipitates a loss of self-tolerance and causes immune-related adverse events (irAEs). We provide a narrative synthesis of the scopes and methods of immunotherapy and mechanisms, clinical presentation, and diagnostic considerations of cardiovascular irAEs while providing real-world examples and perspectives. Recent real-world cases and emerging evidence suggest myocarditis is the most common and potentially fatal cardiovascular irAE, often presenting with symptoms such as shortness of breath or che

BMP-7 Treatment Ameliorates PTEN-Akt Mediated Apoptosis and Adverse Cardiac Remodeling in Ponatinib-Induced Cardiotoxicity.

Background/Objectives: Ponatinib (PON) is a potent anticancer drug widely used to treat chronic myeloid leukemia (CML). Although many cancer survivors benefit from such therapies, managing drug-induced side effects, especially cardiotoxicity, remains a major challenge. Despite its prevalence, the exact mechanisms underlying PON-induced cardiotoxicity have not been thoroughly investigated. Additionally, the potential of Bone Morphogenetic Protein 7 (BMP-7) to alleviate these cardiotoxic effects has yet to be explored. Methods: To address these essential questions, we conducted a study using C57…

Multidimensional perspectives on cancer therapy-induced cardiotoxicity: Characteristics, mechanisms, biomarkers, psychological stress effects, and treatment progress.

Cancer therapy-induced cardiotoxicity (CTIC) is an unavoidable complication in the treatment of cancer patients, an important issue that threatens their quality of life and long-term prognosis. This review comprehensively summarizes the characteristics, mechanisms, biomarkers, psychological stress (PS)-related exacerbation, and therapeutic advances of cancer therapy-induced cardiotoxicity (CTIC) from multidimensional perspectives, covering chemotherapy, targeted therapy, immunotherapy, and radiotherapy. Accumulating evidence demonstrates that distinct cancer therapies induce heterogeneous card…

Stereoselective disruption of copper homeostasis by prothioconazole induces cardiotoxicity via mitochondria-mediated apoptosis in zebrafish embryos.

Chiral pesticides may exhibit enantioselectivity in biological activity, environmental fate, and toxicity. In this study, the enantioselective cardiotoxicity and underlying mechanisms of the chiral fungicide prothioconazole (PTCZ) were thoroughly investigated at the molecular level using zebrafish embryos. Results demonstrated significant stereoselectivity, with S-(+)-PTCZ inducing severe cardiac developmental toxicity, while R-(-)-PTCZ exhibited effects comparable to the control. Mechanistic studies revealed that S-(+)-PTCZ triggered profound copper homeostasis disruption, evidenced by decrea…

Application of 2-Dimensional Speckle Tracking Technology for Trastuzumab-Induced Cardiotoxicity in a New Mouse Model.

OBJECTIVES: To establish a mouse model of trastuzumab-induced cardiotoxicity that aligns with clinical standard treatment protocols, assess the extent of histological damage across various chambers of the mouse heart, and investigate whether 2-dimensional speckle tracking echocardiography (2D-STE) can detect early cardiac dysfunction, while comparing the diagnostic effectiveness of various parameters in cardiotoxicity. METHODS: Mice were randomly assigned to a trastuzumab group (Trz), a doxorubicin-sequential-trastuzumab group (Dox-Trz), and a control group (Con). A mouse model of cardiotoxic…

Ursolic acid ameliorates doxorubicin-induced cardiotoxicity by inhibiting DRP1-mediated excessive mitochondrial fission and oxidative stress.

BACKGROUND: Doxorubicin (DOX) is a commonly used chemotherapeutic agent for treating hematologic malignancies and breast cancer. However, its clinical application is limited by severe cardiotoxicity. Recent studies have suggested that mitochondrial dynamics play a central role in the pathogenesis of doxorubicin-induced cardiotoxicity (DIC). This study was designed to evaluate whether ursolic acid (UA) can mitigate DIC and elucidate the underlying mechanisms related to mitochondrial fission and oxidative stress. METHODS: A chronic DOX-induced cardiotoxicity model was established via the intrap…

A simple and rapid pre-clinical in vivo model reveals comparative cardiotoxicity profiles of kinase inhibitors.

Despite significant success, targeted therapeutics such as kinase inhibitors (KIs) still pose adverse events such as the cardiotoxicity. There is a lot of variation in the type and intensity of cardiotoxicity caused by different KIs and current pre-clinical models are inadequate to predict it. Thus, there is a need to develop more simple and rapid models for screening of novel KIs at the pre-clinical step itself. We thus aimed to establish a rapid and robust pre-clinical animal model for predicting cardiotoxicity of KIs and identify comparative cardiotoxicity profiles of a panel of FDA-approve…

Modulating oxidative stress, apoptosis, and mitochondrial dysfunctions on cardiotoxicity induced by aluminum phosphide pesticide using resveratrol.

The agricultural fumigant pesticide aluminum phosphide (AlP) is cardiotoxic. Water causes AlP to emit phosphine gas, a cardiac toxin that affects heart function and causes cardiogenic shock. AlP poisoning's high fatality rate is due to cardiotoxicity. This study examines how resveratrol reduces oxidative stress, mitochondrial activity, and apoptosis in human cardiac myocyte (HCM) cells. After determining the optimal doses of resveratrol using the MTT test, HCM cells were subjected to a 24-h treatment of resveratrol following exposure to AlP (2.36 μM). The levels of reactive oxygen species (ROS…

Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation.

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluat…