Cardiovascular Toxicology最新文献

Steroids are known to have proarrhythmogenic properties, even though they have been demonstrated to lower the incidence of atrial fibrillation following heart surgery. According to the American Heart Association (AHA), this negative impact was still inconsistent. Therefore, this study aims to elucidate the association between corticosteroid usage and atrial fibrillation.This systematic review employed the keywords "corticosteroids" and "atrial fibrillation," collected from PubMed, Scopus, Web of Science, and Google Scholar. Meta-analysis was performed using a random effects model through Mantel-Haenszel analysis. Disproportionality analysis and Bayesian analysis were conducted utilizing the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) datasets. A narrative review was conducted to obtain mechanistic insights into corticosteroid-induced atrial fibrillation. The meta-analysis of 23 studies involving 679,330 individuals indicated that exogenous steroids elevated the risk of atrial fibrillation by 1.74 times (95% CI = 1.55 to 1.96, p < 0.0001). Intravenous, oral, and inhaled corticosteroids elevated the risk of atrial fibrillation by 2.02, 1.95, and 1.67 times, respectively. The risk of atrial fibrillation was elevated with the administration of corticosteroids at higher doses and for longer durations. Disproportionality analysis from FAERS indicated that some corticosteroids exhibited a significant reported odds ratio (ROR). Corticosteroids can induce mechanical and electrical remodeling of cardiomyocytes, as well as cardiomyocyte senescence, cardiac hypertrophy, hypertension, and diabetes mellitus, all of which may collectively increase susceptibility to atrial fibrillation. Corticosteroids might increase the risk of atrial fibrillation in a dose- and duration-dependent fashion. Inflammation should be regarded as a confounding factor in this conclusion.

Sotatercept (brand name "Winrevair") is a novel activin receptor type IIA (ActRIIA) fusion protein. Sotatercept has received FDA approval for WHO Gloup 1 pulmonary arterial hypertension (PAH) in 2023. While clinical trials demonstrated efficacy, comprehensive real-world safety data are lacking. Food and Drug Adverse Event Reporting System (FAERS) reports from Q1 2024 to Q1 2025 involving Sotatercept were analyzed. After data cleaning and standardization using MedDRA v27.1, reports where Sotatercept was the primary suspect drug (PS) were identified. Disproportionality analysis employed four algorithms: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Onset time analysis was performed. Among 2748 eligible reports, 72.8% involved females, predominantly aged 16-64.9 years. The most frequent System Organ Classes (SOCs) were general disorders and administration site condition (19.29%), gastrointestinal disorders (13.8%), and investigations (13.4%). The first 30 adverse events (AEs) mainly included headache (n = 124), epistaxis (n = 88), hemoglobin increased (n = 81), dizziness (n = 61), and platelet count decreased (n = 42). AEs can still occur after one year of use. This large-scale FAERS analysis identifies signals consistent with known AEs observed during Sotatercept use and identifies novel potential serious safety signals: pulmonary arteriovenous fistula and pericardial effusion. Enhanced monitoring is required, especially of hematologic parameters, bleeding risk, and cardiopulmonary complications during initial treatment. Further investigation into these signals' mechanisms is needed.

Exposure to arsenic (As) is a serious environmental and public health risk because it can cause systemic toxicity, which could lead to serious cardiovascular disease like heart failure, arrhythmias, and coronary heart disease (CHD). Exploring safer and multi-target therapeutic agents is gaining popularity as a result of the shortcomings of traditional therapies. The isoquinoline alkaloid berberine which is derived from plants, exhibits strong anti-inflammatory, antioxidant, and cardioprotective properties. This study employs an integrated network pharmacology and molecular docking approach to investigate the molecular mechanisms and therapeutic potential of berberine in arsenic-induced cardiotoxicity. Key genes target arsenic-induced cardiotoxicity and berberine, have been identified using the Swiss Target Prediction, Gene Cards, OMIM, and CTD databases. A protein-protein interaction (PPI) network was generated by analysing frequently intersecting genes with the STRING and Cytoscape tools. Shiny GO was used to conduct pathway enrichment analysis for the KEGG and Gene Ontology databases. Auto Dock was used to assess berberine's binding affinity. Berberine and arsenic-related cardiotoxicity shared 17 common targets. The primary targets were identified using Cytoscape ABL-1 (2G2F), CDK2 (1HCK), CYP19A1 (3EQM), ICAM-1 (4G6J), KIT (1T45), MAPK14 (3PY3), PGR (1A28), PTGS2 (5F19), RAC1 (3TH5), and SRC (2SRC). Enrichment analysis revealed TNF, VEGF, and AGE-RAGE signaling involvement, all of which are linked to oxidative stress, inflammation, and endothelial dysfunction. Binding affinity between berberine and the target was found to be ABL-1 (-9.2 kcal/mol), PTGS2 (-8.8 kcal/mol), SRC (-8.7 kcal/mol), CYP19A1 (-8.6 kcal/mol), KIT (-8.3 kcal/mol), RAC1 (-7.9 kcal/mol), CDK2 (-7.5 kcal/mol), ICAM-1 (-7.2 kcal/mol), MAPK (-6.8 kcal/mol), PGR (-5.6 kcal/mol). Berberine has multi-targeted therapeutic potential for arsenic-induced cardiotoxicity by modulating inflammatory and oxidative pathways. These results could support the possible usage of berberine in the treatment of cardiovascular diseases caused by arsenic and provide a mechanistic link for further experimental validation.

Cesium chloride (CsCl) is a non-radioactive salt wrongly promoted and used as part of an alternative cancer treatment based on questionable research output published in the mid-eighties. Self-administered cesium can lead to various symptoms. We analyzed the complete set of published case reports of people who have taken cesium to characterize demographics, reasons for intake, clinical effects, reported symptoms, pathophysiology, treatment options, and outcomes, followed by a historical and critical note. A total of 20 cases were included in this literature review. Most patients were females (n = 14), and almost half of the patients were between 40 and 49 years. Most patients used cesium as an alternative treatment for cancer (n = 15). When the route of administration was mentioned, it was most often oral, followed by intravenous use and combined routes. Symptoms occurred across multiple organ systems, including the cardiovascular, neuromuscular and gastrointestinal system. When ECG results were presented, QT prolongation, followed by sinus bradycardia and Torsade de Pointes arrhythmias were most often described. A wide variety of treatments have been provided to the patients. Five patients were reported to have died because of the cesium intake. After absorption, cesium is distributed throughout the body, where it inhibits ion channels, mainly for potassium. These channels, particularly in cardiac cells, are crucial for maintaining normal electrophysiology. The improper promotion of self-administration of cesium as part of an alternative cancer treatment, based on uncorrected scientific misinformation may result in life-threatening cardiac arrhythmia.

Cardiovascular disease is the leading cause of death worldwide, accounting for about a third of all deaths. Traditional risk factors like hypertension, diabetes, dyslipidemia, and obesity are well known, but iron also plays a crucial role in heart health. Iron is essential for oxygen transport, mitochondrial function, and heart muscle activity, and both deficiency and overload can harm cardiovascular outcomes. This review examines studies on iron metabolism, regulation via the hepcidin-ferroportin pathway, myocardial energy, oxidative stress, and clinical trials of iron supplementation or reduction in heart failure, chronic kidney disease, the elderly, women, and athletes. Iron deficiency affects over 60% of heart failure patients, leading to reduced energy, lower exercise capacity, and higher morbidity. Intravenous iron improves functional capacity, quality of life, and reduces hospitalizations, especially in patients with low transferrin saturation. Iron overload, on the other hand, increases oxidative stress, arrhythmias, and cardiomyopathy. Evidence shows a U-shaped relationship between iron and cardiovascular outcomes, emphasizing the importance of markers like transferrin saturation, soluble transferrin receptor, and hepcidin. Iron imbalance contributes to cardiovascular disease. Targeted assessment and treatment, including supplementation for deficiency and chelation or phlebotomy for overload, may improve outcomes. The ultimate aim of this review is to enhance perioperative management and long-term results for this highly vulnerable population by synthesizing current insights and addressing knowledge gaps.

Accumulating evidence supports the association between endocrine disrupting chemicals (EDCs) exposure and cardiovascular disease (CVD). However, the link between EDCs and cardiovascular health (CVH) prior to CVD onset remains unclear. This study investigates the relationship between individual and combined EDC exposure and Life's Essential 8 (LE8). We included 9,940 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2003 and 2016, excluding adults with known CVD. Twenty-two types of EDCs were detected in urine samples, including three phenols, two phenolic pesticides, eleven phthalates, and six polycyclic aromatic hydrocarbons (PAHs). Weighted generalized linear models (GLM) and weighted quantile sum (WQS) regression to explore the relationship between single/mixed exposure to EDCs and CVH. Overall, 9,940 individuals (weighted mean [SE] age, 42.53 [0.26] years; 5,313 women [weighted 53.7%]) without CVD were included, with a mean score of LE8 at 68.70. The GLM model reveals that specific exposures to EDCs are inversely associated with LE8, serving as independent risk factors contributing to poorer CVH. The WQS index of EDCs was independently associated with overall CVH, with an adjusted odds ratio (OR) of 3.00 (95% confidence interval [CI]: 2.30-3.90; P < 0.001). 2-Fluorenone (2-FLU) emerged as the most heavily weighted component in the overall CVH model. This study emphasizes the association between exposure to EDCs is correlated with a higher odds ratio for decline in CVH among American adults. 2-FLU emerges as a prominent contributor. It provides epidemiologic evidence for the detrimental effects of these chemicals on CVH.

Cadmium (Cd), a widespread environmental contaminant, induces cardiotoxicity even at low doses through endocrine disruption and oxidative stress. This investigation assessed age-related susceptibility in female albino rats by comparing pre-pubertal (30-day-old) and post-pubertal (60-day-old) animals that were administered CdCl₂ at a dosage of 5.12 mg/kg body weight per day via oral gavage for 15 days. Despite greater Cd accumulation in pre-pubertal rats, post-pubertal animals exhibited heightened cardiac injury. This paradox correlated with impaired induction of metallothionein (MT), enhanced glutathione and vitamin C depletion, and reduced enzymic antioxidants (SOD, CAT, GPx). Concomitantly, altered adrenal function with increased corticosterone (CORT) and reduced estradiol (E2) reflected differential hypothalamic-pituitary-adrenal (HPA) axis responsiveness, further compromising antioxidant defenses. Biomarkers of cardiac function confirmed this vulnerability: increased serum CK-MB and troponin I, electrocardiographic (ECG) abnormalities (ST elevation, QT prolongation, tachycardia), and larger infarct volume. Collectively, these findings demonstrate that post-pubertal susceptibility is driven by reduced MT inducibility and HPA axis-mediated endocrine dysregulation, which amplify oxidative injury and structural remodeling of ventricular myocardium. From a translational standpoint, our findings identify adolescence and early adulthood as critical windows during which females exhibit heightened vulnerability to environmental CdCl₂ exposure. Variations in metallothionein (MT) expression capacity and estradiol levels may serve as informative biomarkers for predicting individual susceptibility. These results also suggest the potential value of targeted interventions such as MT induction, antioxidant therapy, or modulation of hormonal pathways, that merit further investigation. Collectively, the study emphasizes the urgent need for stricter regulation of cadmium exposure, particularly among peripubertal populations, to reduce lifelong cardiovascular risk.