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Mechanistic Insights into the Cardiotoxic Effects of Dextromethorphan and Its Metabolite Dextrorphan in Zebrafish Using Network Toxicology and Molecular Dynamics.

The high incidence of respiratory diseases has driven a substantial increase in the use of antitussive dextromethorphan (DXM), leading to the frequent detection of its primary human metabolite, dextrorphan (DXO), in aquatic environments. However, existing research has paid limited attention to the toxic effects of DXM and its metabolite, DXO, on fish. In this study, zebrafish embryos were exposed to DXM and DXO at concentrations ranging from 100 to 10,000 ng/L for 72 hours post-fertilization (hpf) to evaluate their impacts on cardiac function and elucidate underlying molecular mechanisms using

Cardiotoxicity of newer HER2-Directed therapies in breast cancer: A systematic review and meta-analysis of incidence and comparative risk.

PURPOSE: This systematic review and meta-analysis aimed to estimate the incidence and comparative risk of cardiotoxicity associated with newer HER2-targeted therapies compared with conventional trastuzumab-based regimens. It also evaluates the differences across drug classes, clinical subgroups, and monitoring strategies. MATERIALS AND METHODS: PubMed, Embase, CENTRAL, and Scopus were searched (2005-2025) for randomized controlled trials (RCTs) and prospective studies reporting cardiac outcomes with HER2-directed therapies. Pooled cardiotoxicity incidence was calculated from single-arm studie…

[Cardiotoxicity in children and adolescents with acute leukemia: Recommendations from the Leukemia Committee of the French Society of Childhood Cancer (SFCE)].

Cardiotoxicity from anti-leukemic therapies remains a major concern in pediatric hemato-oncology - often subclinical in the short term but potentially life-threatening in the long term. In children, who are exposed to cardiotoxic treatments at an early age and have long life expectancies, a proactive strategy for prevention, early detection, and management is essential. Anthracyclines remain a cornerstone of pediatric acute leukemia treatment but are associated with a risk of heart failure in approximately 10% of cases, particularly at cumulative doses exceeding 300mg/m2 of doxorubicin-equival…

Early Cardiotoxic Remodelling Precedes Hepatic Fibrosis and Increases Susceptibility to Lethal Arrhythmias in Wild-Type MASH Mice.

OBJECTIVE: Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly linked to cardiovascular complications; however, the mechanisms underlying the association between hepatic injury and cardiotoxicity remain unclear. This study aimed to establish a wild-type mouse model of MASH with cardiac involvement and to characterise the temporal relationship between hepatic and cardiac alterations during disease progression. METHODS: Male C57BL/6J mice were fed a standard diet or a low-carbohydrate, high-protein, high-cholesterol (LCHP-HC) diet with or without non-excessive ethanol for 12…

Biochanin A attenuates doxorubicin-induced cardiotoxicity in rats with associated modulation of PI3K/Akt/mTOR and p38 MAPK signaling.

BACKGROUND: Doxorubicin (DOX) is an effective anthracycline chemotherapeutic agent, but its clinical use is limited by dose-dependent cardiotoxicity associated with oxidative stress, inflammation, and apoptosis. Biochanin A (BCA), an O-methylated isoflavone, has demonstrated antioxidant and anti-inflammatory properties. OBJECTIVES: This study investigated whether BCA could mitigate DOX-induced cardiac injury in rats and explored the underlying molecular mechanisms. METHODS: Male Wistar rats were randomly assigned to control, BCA-alone, DOX-alone, and DOX combined with BCA (25 or 50 mg/kg) gr…

Insights into the disinfection byproduct bromochloroacetamide-induced cardiotoxicity of zebrafish embryo-larvae: A multiomics approach and comparison of biomarker responsiveness.

Bromochloroacetamide (BCAcAm), an inevitable byproduct of the water treatment disinfection process, is widely detected in drinking water. Pr … of Fer-1 (a ferroptosis inhibitor) reversed BCAcAm-induced mitochondrial dysfunction and subsequent cardiotoxicity. In addition, the BMD and IBRv2 indices were derived from molecules across various biological levels. The general ranking of the different biomarkers in terms of better responsiveness and sensitivity performance is as follows: transcriptomics > meta …

A PI3K Inhibitor with Low Cardiotoxicity and Its Synergistic Inhibitory Effect with Gilteritinib in Acute Myelogenous Leukemia (AML) Cells.

N-(2-chloro-5-(3-(pyridin-4-yl)-1H-pyrazolo [3,4-b]pyridin-5-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide, namely, FD274, is a promising 7-azaindazole-based PI3K inhibitor candidate with high antitumor efficacy against acute myeloid leukemia and reduced cardiotoxicity in the zebrafish model. To advance its clinical translation, in this work, we conducted comprehensive assessments of the cardiotoxicity of FD274 and preliminarily investigated its synergistic antitumor effects with an FLT3 inhibitor, Gilteritinib. The cardiotoxicity profile of FD274, as well as its bioisostere FD268 (positive cont…

Pharmacological interventions for anthracycline-induced cardiotoxicity in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This study aimed to systematically assess the efficacy of cardioprotective agents in preventing anthracycline-induced cardiotoxicity in patients with breast cancer using a comprehensive network meta-analysis (NMA). METHODS: This study included patients with breast cancer undergoing anthracycline-based chemotherapy. Randomized controlled trials (RCTs) published before March 2020 were identified through systematic searches in MEDLINE, Cochrane CENTRAL, Web of Science, and CINAHL. The primary outcome was left ventricular ejection fraction (LVEF), assessed using cardiac magnetic resonanc…

Radiation Oncology Opinions and Practice on Cardiotoxicity in Lung Cancer: A Cross-sectional Study by the International Cardio-oncology Society.

AIMS: Symptomatic radiation cardiotoxicity affects up to 30% patients with lung cancer and several heart substructure doses are associated with reduced overall survival. A greater focus on minimising cardiotoxicity is now possible due to advancements in radiotherapy technology and the new discipline of cardio-oncology, but uptake of emerging data has not been ascertained. A global cross-sectional analysis of Radiation Oncologists who treat lung cancer was therefore conducted by the International Cardio-Oncology Society in order to establish the impact of recently published literature and guide…

Metabolomics with gut microbiota analysis of podophyllotoxin-mediated cardiotoxicity in mice based on the toxicological evidence chain (TEC) concept.

Podophyllotoxin (PPT) is a lignan isolated from the traditional Chinese medicine Dysosma Versipellis, with significant anti-tumor activity. However, its cardiotoxicity restricts its clinical application. This study aims to investigate the cardiotoxicity of PPT in mice and its underlying mechanisms based on the concept of toxicological evidence chain (TEC). In this study, alterations in body weight, behavior, and the levels of myocardial enzymes and histopathology in mice were observed. Additionally, microbiome and metabolome were integrated to identify potential microorganisms, metabolic marke…

Electrocardiographic, biochemical, and scintigraphic evidence for the cardioprotective effect of paricalcitol and vitamin D3 on doxorubicin-induced acute cardiotoxicity in rats.

AIM: We aimed to investigate the possible cardioprotective effects of paricalcitol (PR), its vitamin D receptor agonist, and vitamin D3 (VIT-D3) on an experimental model of doxorubicin (DX) cardiotoxicity by 99mTc-PYP scintigraphy, electrocardiographic (ECG) and biochemical methods. METHOD: Forty-two male Wistar/Albino rats (250‒300 g; aged 10‒12 weeks) were randomly separated into six groups, namely into control (CN), doxorubicin (DX), paricalcitol (PR), vitamin D3 (VIT-D3), paricalcitol + doxorubicin (PR+DX), and vitamin D3 + doxorubicin (VIT-D3+DX) groups. Cardiotoxicity was induced by thr…

Efficacy and harms associated with β-blockers for cardiotoxicity in cancer patients undergoing chemotherapy: a systematic review and meta-analysis.

INTRODUCTION: In patients with breast cancer and lymphoma, anthracyclines are associated with early and late dose-related cardiotoxicity. We systematically evaluated the efficacy and harms of the use of β-blockers in breast cancer and lymphoma patients undergoing chemotherapy. MATERIAL AND METHODS: We searched five engines, and pre-prints until October 10, 2022, for randomized controlled trials (RCTs) evaluating β-blockers for anthracycline-associated cardiotoxicity in breast cancer and lymphoma patients. Primary outcomes were all-cause mortality, left ventricular ejection fraction (LVEF), le…

Cardiotoxicity of HER2-Targeted Drugs When Combined with Other Drugs: A Systematic and Meta-analysis of Randomized Controlled Trials.

The development and use of HER2-targeted drugs has improved the prognosis of HER2-positive cancer patients. However, in addition to improved survival rates, treatment-induced adverse events and nontumor-related deaths have increased. We sought to assess the incidence of cardiovascular adverse events when HER2-targeted drugs are combined with other drugs. We systematically searched the literature on the cardiotoxicity of anti-HER2 drugs in electronic databases, including PubMed, Web of Science, Cochrane Library, OVID and CNKI, from their inception to April 2022. The Cochrane Collaboration's too…

A Review on Probable Causes of Cardiotoxicity Caused by Common Cancer Drugs and the Role of Traditional Chinese Medicine in Prevention and Treatment.

Cancer is a widespread disease in our nation, characterized by a high occurrence rate. The use of tumor medications has been linked to an increased chance of cardiovascular complications, including a notable occurrence of heart toxicity. This has caused significant concern among healthcare professionals. This article provides a comprehensive compilation of drugs recognized for their potential to cause heart toxicity. Furthermore, extensive research has been conducted to investigate and categorize the effects of heart toxicity, with the purpose of promoting awareness, facilitating early interve

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… Studies have revealed that subclinical cardiotoxicity caused by chemotherapy drugs affects up to 18% of patients, while clinical cardiotoxicity occurs in as many as 6% of cases. 3 The emergence of cardiotoxicity as a side effect of chemotherapy drugs poses a new challenge in terms of clinical diagnosis … The cardiotoxicity of macrolides: a systematic review. Pharmazie . 2010;65(9):631–640. 58. Bhagat A, Kleinerman ES. Anthracycline-Induced Cardiotoxicity: causes, Mechanisms, and Prevention. Adv Exp Med Biol . 2020;1257:181–192. …

Comparison of bolus administration and short-term infusion versus long-term infusion of doxorubicin in terms of cardiotoxicity and efficacy.

Cardiotoxicity caused by anthracyclines chemotherapy is one of the leading causes of mortality and morbidity in cancer survivors. Continuous infusion (CI) instead of bolus (BOL) injection is one of the methods that seem to be effective in reducing doxorubicin (DOX) cardiotoxicity. Due to the variety of results, we decided to compare these two approaches regarding toxicity and efficacy and report the final results for different cancers. We included 21 studies (four preclinical and seventeen clinical trials) up to May 15, 2023. In children with acute lymphoblastic leukemia (ALL) and adults with …

Estimation of time since death using cardiac troponin I in case of death due to asphyxia and cardiotoxicity of acebutolol.

The objective of this study was to investigate the degradation pattern of cardiac troponin I in rats in vivo, and to determine whether the pattern was dependent on the cause of death, for the purpose of estimating the postmortem interval. The rats were categorized into three distinct groups depending on the factors leading to their demise: the control group, the group experiencing acebutolol-induced cardiotoxicity, and the group affected by asphyxia. The analysis encompassed the isolation and segregation of the protein, subsequently employing Western blotting as a means of visualizing the resu…

The new HFA/ICOS risk assessment tool to identify patients with chronic myeloid leukaemia at high risk of cardiotoxicity.

AIMS: Tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukaemia (CML) can cause cardiovascular adverse events. So far, the Systematic Coronary Risk Evaluation (SCORE) charts of the European Society of Cardiology (ESC) have been used to identify cancer patients at increased cardiovascular risk. The primary aim of our study was to evaluate the usefulness of the new cardiovascular risk assessment model proposed by the Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the ESC in collaboration with the International Cardio-Oncology Society (ICOS) to stratify the

pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects.

The delivery of therapeutics into sites of action by using cargo-delivery platforms potentially minimizes their premature degradation and fast clearance from the bloodstream. Additionally, drug-loaded stimuli-responsive supramolecular assemblies can be produced to respond to the inherent features of tumor microenvironments, such as extracellular acidosis. We report in this framework the use of pH-responsive polymersomes (PSs) manufactured using poly([N-(2-hydroxypropyl)] methacrylamide)35-b-poly[2-(diisopropylamino)ethyl methacrylate]75 as the building unit (PHPMA35-b-PDPA75). The self-assembl

Protective Role of Vitamin B1 in Doxorubicin-Induced Cardiotoxicity in Rats: Focus on Hemodynamic, Redox, and Apoptotic Markers in Heart.

Up until now, the specific mechanisms involved in doxorubicin (DOX)-induced cardiotoxicity have not been fully elucidated. Since thiamine deficiency is associated with myocardial dysfunction and it may lead to cardiomyopathy, we aimed to investigate whether thiamine (Vitamin B1) treatment provides cardioprotection and modulates DOX mediated subchronic cardiotoxicity as well as to determine possible mechanisms of its effects. The study involved 48 Wistar albino rats divided into four groups: healthy non-treated rats and healthy rats treated with thiamine and DOX rats without treatment and DOX r…