Cardiovascular Toxicology最新文献

Association Between ABCG2 Polymorphism and Statin-Induced Adverse Events: A Meta-Analysis. ABCG2多态性与他汀类药物引起的不良事件之间的关系：一项荟萃分析。

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-08-23 DOI: 10.1007/s12012-025-10056-w

Da Hoon Lee, Hae Ji Shin, Beom Yoon, Han Wool Kim, Hyeon Woo Jo, Hee Jung Kim, Woorim Kim

{"title":"Association Between ABCG2 Polymorphism and Statin-Induced Adverse Events: A Meta-Analysis.","authors":"Da Hoon Lee, Hae Ji Shin, Beom Yoon, Han Wool Kim, Hyeon Woo Jo, Hee Jung Kim, Woorim Kim","doi":"10.1007/s12012-025-10056-w","DOIUrl":"10.1007/s12012-025-10056-w","url":null,"abstract":"Statins, widely used for preventing cardiovascular diseases due to their cholesterol-lowering effects, are associated with potential adverse reactions in some individuals, underscoring the need to understand the factors contributing to statin-related complications. The ATP-binding cassette subfamily G member 2 (ABCG2) gene, which encodes a multidrug transporter, has garnered attention due to its involvement in statin metabolism. Specifically, the rs2231142 polymorphism within ABCG2 has been implicated in altered drug metabolism and pharmacokinetics, potentially influencing statin-related toxicity. Despite previous investigations, findings regarding this association remain inconclusive. Thus, this systematic review and meta-analysis aimed to clarify the correlation between the rs2231142 polymorphism and statin-induced toxicity. Through a comprehensive literature search, seven eligible studies were identified and subjected to rigorous data extraction and quality assessment. Meta-analysis revealed a significant association between the rs2231142 polymorphism and an increased risk of overall statin-induced toxicity, including muscular and hepatic toxicity, with odds ratios of 2.6 and 2.7, respectively. These findings suggest a potential role for ABCG2 polymorphisms in statin-related adverse events and emphasize the importance of personalized treatment strategies in managing statin therapy.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1761-1767"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chrysin Attenuates Myocardial Cell Apoptosis in Mice. 菊花素减缓小鼠心肌细胞凋亡。

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-09-06 DOI: 10.1007/s12012-025-10058-8

Gang Deng, Yongzheng Yang, Ouyang Qing, Jiang Linhui, Su Haotao, Chi Liu, Ge Li, Moussa Ide Nasser

{"title":"Chrysin Attenuates Myocardial Cell Apoptosis in Mice.","authors":"Gang Deng, Yongzheng Yang, Ouyang Qing, Jiang Linhui, Su Haotao, Chi Liu, Ge Li, Moussa Ide Nasser","doi":"10.1007/s12012-025-10058-8","DOIUrl":"10.1007/s12012-025-10058-8","url":null,"abstract":"Myocardial infarction (MI), induced by ischemia and hypoxia of the coronary arteries, presents as myocardial necrosis. Patients often experience intense, prolonged retrosternal pain that is unrelieved by rest or nitrate therapy and is frequently associated with high blood myocardial enzyme levels. Physical effort may exacerbate this anxiety, increasing the likelihood of life-threatening consequences such as arrhythmias, shock, or cardiac failure. Chrysin, a natural flavonoid primarily found in honey and propolis, exhibits anti-inflammatory, antioxidant, anticancer, and antiviral properties. This study utilized MI models and various analytical techniques, including Western blotting, immunofluorescence, quantitative polymerase chain reaction (qPCR), and autodocking, to elucidate the molecular mechanisms underlying the action of chrysin in molecular interactions. Our results demonstrated that Chrysin alleviates apoptosis in cardiomyocytes by decreasing the Bax/Bcl-2 ratio and suppressing caspase-3 activation, actions facilitated by PPAR-γ activation and consequent overexpression of anti-apoptotic proteins. Furthermore, chrysin mitigates cardiac fibrosis by downregulating TGF-β1, collagen I, and α-SMA expression. These effects markedly diminish infarct size and improve heart function in ischemia-reperfusion damage models, ascribed to chrysin's activation of PPAR-γ and SIRT3, together with the regulation of β-catenin pathways. The preclinical data presented in this research establish a foundation for forthcoming clinical studies to assess the safety and effectiveness of chrysin in patients with myocardial infarction. This may facilitate the development of a novel treatment approach for treating MI.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1791-1806"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TNFAIP8 Deficiency Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Inflammation Via TLR4/NF-κB Signaling. TNFAIP8缺乏通过TLR4/NF-κB信号抑制氧化应激和炎症，减轻阿霉素诱导的心脏毒性。

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-09-20 DOI: 10.1007/s12012-025-10061-z

Ling Chen, Jian Wu, Hongjie Yang, Jijun Liu, Yang Yu

{"title":"TNFAIP8 Deficiency Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Inflammation Via TLR4/NF-κB Signaling.","authors":"Ling Chen, Jian Wu, Hongjie Yang, Jijun Liu, Yang Yu","doi":"10.1007/s12012-025-10061-z","DOIUrl":"10.1007/s12012-025-10061-z","url":null,"abstract":"Doxorubicin-induced cardiotoxicity (DIC) is pathologically characterized by oxidative stress and inflammatory cascades, creating an urgent need to identify therapeutic targets modulating these processes. While tumor necrosis factor alpha-induced protein 8 (TNFAIP8) has emerged as a regulator of inflammation and apoptosis, its functional role in DIC remains unexplored. This study systematically investigates TNFAIP8's cardioprotective mechanisms against DIC. A chronic DIC model was established in male C57BL/6 mice through intraperitoneal doxorubicin (DOX) administration (4 mg/kg weekly for 4 weeks; cumulative dose 16 mg/kg). TNFAIP8 knockdown was achieved via AAV9-delivered shRNA through tail vein injection. Multimodal assessment integrating echocardiography, histopathology analysis, and molecular profiling elucidated TNFAIP8's functional and mechanistic contributions. In DOX-induced cardiomyocytes, TNFAIP8 expression was upregulated. The absence of TNFAIP8 markedly reduced DOX-triggered oxidative stress and inflammatory responses. The potential protective mechanism of TNFAIP8 deficiency against DIC involves toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Importantly, administration of the TLR4 activator lipopolysaccharide (LPS) substantially reversed the cardioprotective effects observed with TNFAIP8 deletion. Our findings establish TNFAIP8 as a critical regulator of DIC pathophysiology through TLR4/NF-κB axis modulation. Pharmacological TNFAIP8 inhibition represents a viable therapeutic strategy for mitigating chemotherapy-induced cardiac dysfunction. Future investigations should prioritize developing cardiac-targeted TNFAIP8 inhibitors and validating their efficacy in large-animal DIC models.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1718-1731"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the Impact of E-cigarettes on Cardiovascular Health: Insights from Preclinical and Clinical Studies. 探索电子烟对心血管健康的影响：来自临床前和临床研究的见解。

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-08-19 DOI: 10.1007/s12012-025-10046-y

Tijana Simovic, Chloe L Matheson, Marisa Colon, Caroline O Cobb, Judith Voynow, Youngdeok Kim, Patrick Nana-Sinkam, Ryan Garten, Paula Rodriguez-Miguelez

{"title":"Exploring the Impact of E-cigarettes on Cardiovascular Health: Insights from Preclinical and Clinical Studies.","authors":"Tijana Simovic, Chloe L Matheson, Marisa Colon, Caroline O Cobb, Judith Voynow, Youngdeok Kim, Patrick Nana-Sinkam, Ryan Garten, Paula Rodriguez-Miguelez","doi":"10.1007/s12012-025-10046-y","DOIUrl":"10.1007/s12012-025-10046-y","url":null,"abstract":"Electronic cigarettes are popular tobacco products that heat e-liquid into an aerosol for inhalation. Since their introduction to the market, electronic cigarettes have been considered a safer alternative to combustible tobacco products. However, most of today's users are adolescents and young adults naïve to tobacco products, who are drawn to e-cigarettes by appealing designs and targeted marketing, resulting in exposure to largely unknown short- and long-term health risks. While the cardiovascular effects of electronic cigarettes remain incompletely understood, there has been a growing concern surrounding their potential acute and chronic impact on cardiovascular health and disease risks. In this review, we examine the components of e-cigarettes and evaluate the cardiovascular effects of both acute and regular e-cigarette exposure, summarizing findings from existing preclinical and clinical studies to provide a comprehensive overview about the topic.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1673-1688"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12513945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Role of Endocrine Disrupting Chemicals in the Development of Atherosclerosis. 内分泌干扰物在动脉粥样硬化发生中的作用。

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-08-17 DOI: 10.1007/s12012-025-10054-y

Aysen Kutan Fenercioglu, Durisehvar Ozer Unal

{"title":"The Role of Endocrine Disrupting Chemicals in the Development of Atherosclerosis.","authors":"Aysen Kutan Fenercioglu, Durisehvar Ozer Unal","doi":"10.1007/s12012-025-10054-y","DOIUrl":"10.1007/s12012-025-10054-y","url":null,"abstract":"Endocrine disrupting chemicals (EDCs) are exogenous compounds that interfere with the normal functioning of the endocrine system. This effect is crucial for maintaining hormonal balance and regulating various physiological processes. Phthalates, parabens, and triclosan are EDCs found in many personal care products (make-up, shampoo, perfume, shaving foam, moisturizing cream, hair dyes, deodorant), plastics, pesticides, pharmaceuticals, and household cleaning products, and can be inhaled or absorbed by the body through inhalation or skin contact. Atherosclerosis is a major cause of cardiovascular diseases, including coronary artery disease, stroke, and peripheral artery disease. While traditional risk factors for atherosclerosis, such as high cholesterol, hypertension, and smoking, have been extensively studied, emerging evidence suggests that EDCs may also play a significant role in the development and progression of atherosclerosis. Several potential mechanisms have been proposed to explain how EDCs contribute to atherosclerosis. One mechanism involves the activation of nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) and estrogen receptors (ERs), by EDCs. Activation of these receptors can lead to dysregulation of lipid metabolism, inflammation, and oxidative stress, all of which are key processes in atherosclerosis development. EDCs have been shown to disrupt endothelial function through various mechanisms. Some of these mechanisms are the formation of reactive oxygen species (ROS) and free oxygen radicals, and impaired nitric oxide (NO) production by EDCs. This literature review aims to explore the current understanding of the role of EDCs in atherosclerosis.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1706-1717"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prediction of QTc Prolongation in Acute Poisoning with Atypical Antipsychotics Using Machine Learning Techniques: A Study from Poison Control Center. 应用机器学习技术预测非典型抗精神病药物急性中毒患者QTc延长：来自中毒控制中心的研究。

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-08-30 DOI: 10.1007/s12012-025-10055-x

Asmaa Fady Sharif, Ahmad Hafez, Manar Maher Fayed, Zahraa Khalifa Sobh

{"title":"Prediction of QTc Prolongation in Acute Poisoning with Atypical Antipsychotics Using Machine Learning Techniques: A Study from Poison Control Center.","authors":"Asmaa Fady Sharif, Ahmad Hafez, Manar Maher Fayed, Zahraa Khalifa Sobh","doi":"10.1007/s12012-025-10055-x","DOIUrl":"10.1007/s12012-025-10055-x","url":null,"abstract":"Atypical antipsychotics have experienced a significant increase in use across various disorders, coinciding with a rise in acute intoxication. This retrospective study predicts prolonged QTc interval and the necessity for mechanical ventilation (MV) in patients with acute atypical antipsychotic poisoning using machine learning techniques. This retrospective study included 355 patients with a mean age of 26.1 ± 9.6 years. The overall prevalence of the investigated outcomes was 5.5% for prolonged QTc interval and 7.1% for MV. Eight classifiers were developed, including Logistic Regression, Support Vector Machine, K-Nearest Neighbors, and five tree-based models: Random Forest, XGBoost, LightGBM, CatBoost, and Gradient Boosting Models. Model validation was conducted through external validation using the testing dataset and an internal five-fold cross-validation after optimizing the hyperparameters. As a predictor of prolonged QTc interval, all tree-based models achieved perfect specificity, recall, precision, accuracy, and area under the curve (AUC) of 100% using the training dataset. Similar performance was reported in models predicting the necessity for MV. Upon validation, the tree-based models for predicting prolonged QTc intervals maintained good AUCs, ranging between 0.930 and 0.958 in the training dataset and between 0.927 and 0.949 in the testing dataset. In terms of accuracy, the tree-based models exhibited good values in both external and five-fold cross-validation, with all values above 0.901. The observed declines in recall and precision during the validation of the proposed models underscore the need for future studies to utilize larger validation cohorts, thereby enabling the generalization of the proposed models in relevant clinical settings.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1732-1753"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cold Inducible RNA-Binding Protein: A Novel Therapeutic Target for Ventricular Arrhythmia Control. 冷诱导rna结合蛋白：控制室性心律失常的新治疗靶点。

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-08-31 DOI: 10.1007/s12012-025-10057-9

Nan Wu, Caijie Shen, Jian Wang, Yingchu Hu, Tingsha Du, Xiaomin Chen, Peng Zhong

{"title":"Cold Inducible RNA-Binding Protein: A Novel Therapeutic Target for Ventricular Arrhythmia Control.","authors":"Nan Wu, Caijie Shen, Jian Wang, Yingchu Hu, Tingsha Du, Xiaomin Chen, Peng Zhong","doi":"10.1007/s12012-025-10057-9","DOIUrl":"10.1007/s12012-025-10057-9","url":null,"abstract":"Ventricular arrhythmias following myocardial infarction (MI) remain a leading cause of sudden cardiac death, yet therapeutic options are limited by incomplete understanding of the molecular mechanisms governing post-infarction arrhythmogenesis. While RNA-binding proteins have emerged as critical regulators of cardiovascular pathophysiology, their role in cardiac electrophysiology remains largely unexplored. Here, we demonstrate that cold- inducible RNA-binding protein (CIRP) functions as a critical regulator of ventricular arrhythmia susceptibility through post-transcriptional control of cardiac ion channels. In a rat MI model, cardiac-specific CIRP overexpression was achieved using AAV9 gene delivery under cTNT promoter control, followed by LAD ligation. Our results show that CIRP gene therapy significantly reduced ventricular arrhythmia inducibility in programmed electrical stimulation studies and improved cardiac function parameters. Electrophysiological analysis revealed that CIRP prolonged action potential duration through selective post-transcriptional downregulation of Kv4.2 and Kv4.3 potassium channel proteins without altering mRNA levels. This post-transcriptional mechanism represents a novel pathway linking temperature-responsive RNA regulation to electrophysiological stability. Western blot and RT-PCR analysis confirmed protein-specific suppression of target ion channels in CIRP-treated hearts. These results establish CIRP as a critical mediator in the post-transcriptional regulatory network governing cardiac rhythm and identify RNA-binding protein modulation as a promising therapeutic strategy for post-MI arrhythmia prevention. This mechanistic insight opens new avenues for understanding how cellular stress responses influence cardiac electrophysiology and may inform the development of next-generation antiarrhythmic therapies.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1768-1779"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hormone Receptor Expression and QT interval at Baseline Correlate with Trastuzumab Associated Cardiotoxicity in HER2- Positive Breast Cancer Patients: A Prospective Study. HER2阳性乳腺癌患者基线激素受体表达和QT间期与曲妥珠单抗相关心脏毒性相关：一项前瞻性研究

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-09-19 DOI: 10.1007/s12012-025-10059-7

Dana Abo Samra, Ibrahem Hanafi, Dani Abo Samra, Ahmad Naeem, Assef Dayyoub

{"title":"Hormone Receptor Expression and QT interval at Baseline Correlate with Trastuzumab Associated Cardiotoxicity in HER2- Positive Breast Cancer Patients: A Prospective Study.","authors":"Dana Abo Samra, Ibrahem Hanafi, Dani Abo Samra, Ahmad Naeem, Assef Dayyoub","doi":"10.1007/s12012-025-10059-7","DOIUrl":"10.1007/s12012-025-10059-7","url":null,"abstract":"Trastuzumab is a common and effective therapeutic choice for breast cancer treatment. However, the cardiotoxicity induced by this therapy remains a significant challenge, because we lack predictors that help avoid allocating some patients with high risk to this management plan. This study was aimed to evaluate several baseline risk factors such as prolonged QTc interval, age, and lower expression level of estrogen and progesterone receptors that might predict cardiac toxicity after Trastuzumab therapy. This prospective observational study was conducted in Al-Bairouni Hospital at Damascus University. Patients were evaluated with echocardiography and electrocardiography before therapy and three weeks after the last administration of the fourth cycle. A significant Trastuzumab-related cardiotoxicity was determined by a 5% or more reduction in the left ventricular ejection fraction after excluding all other potential causes. A total number of 140 patients with breast cancer, who were indicated Trastuzumab therapy, were recruited for this study. Thirty of them (21.4%) developed Trastuzumab-related cardiotoxicity but all were asymptomatic. Corrected QT interval of more than 450 ms and lower expression level of estrogen and progesterone receptors at baseline were associated with higher susceptibility to develop Trastuzumab-related cardiotoxicity (P = 0.045, P = 0.004, and P = 0.042, respectively). Of note, preexisting cardiac morbidities, age, and chemotherapy accompanying Trastuzumab administration did not reach significant association with cardiotoxicity. Breast cancer patients with prolonged corrected QT interval or lower expression levels of hormone receptors are at a higher risk of developing Trastuzumab-related cardiotoxicity, necessitating careful administration of the therapy.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1754-1760"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Uric Acid Disrupts Heart Development in Zebrafish by Inhibiting the Wnt Signaling Pathway. 尿酸通过抑制Wnt信号通路干扰斑马鱼心脏发育。

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-08-21 DOI: 10.1007/s12012-025-10053-z

Yahong Li, Peiying Yang, Xin Wang, Zhilei Zhang, Tao Jiang, Yun Sun, Zhengfeng Xu

{"title":"Uric Acid Disrupts Heart Development in Zebrafish by Inhibiting the Wnt Signaling Pathway.","authors":"Yahong Li, Peiying Yang, Xin Wang, Zhilei Zhang, Tao Jiang, Yun Sun, Zhengfeng Xu","doi":"10.1007/s12012-025-10053-z","DOIUrl":"10.1007/s12012-025-10053-z","url":null,"abstract":"Congenital heart disease (CHD) is the most common birth defect and involves intricate developmental mechanisms. Uric acid (UA), the final metabolite of purine degradation in humans, has a largely unexplored role in heart development. This study investigated the effects of elevated UA levels-both exogenous and endogenous-on cardiac development in a zebrafish model and explored the involvement of Wnt signaling in this process. UA elevation was achieved through exogenous UA exposure, in vivo overexpression of xdh, and knockdown of uox. Expression levels of Wnt pathway components (wnt1, wnt3a, wnt6b, and β-catenin), cardiac progenitor markers (mesp1 and isl1), neural crest cell markers (sox10 and crestin), and cardiac development genes (nkx2.5, tbx5a, and fgf10a) were assessed at key developmental stages. All UA-elevating strategies significantly increased UA concentrations and led to phenotypes including pericardial edema and reduced heart rate at 72 h post-fertilization (hpf). These phenotypes were accompanied by downregulation of Wnt signaling and cardiac development genes. Treatment with the Wnt activator CHIR99021 partially rescued the cardiac defects induced by UA overload. These findings demonstrate that elevated UA-whether exogenous or endogenous-can disrupt cardiac development in zebrafish, at least in part by suppressing Wnt signaling, thereby impairing downstream gene networks essential for heart morphogenesis.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1689-1705"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vanillic Acid Mitigates Mitochondrial Dysfunction Induced by Lithium via Maintenance of Mitochondrial Function, Inhibition of Oxidative Stress, and Mitochondrial Swelling in Rat Heart-Isolated Mitochondria. 香草酸通过维持线粒体功能、抑制氧化应激和线粒体肿胀减轻锂诱导的线粒体功能障碍。

IF 3.7 3区医学

Cardiovascular Toxicology Pub Date : 2025-11-01 Epub Date: 2025-09-15 DOI: 10.1007/s12012-025-10060-0

Mir-Jamal Hosseini, Milad Hossein Zadeh, Mohammad Shabani, Vahed Adhami, Hanieh Delavari, Ahmad Salimi

{"title":"Vanillic Acid Mitigates Mitochondrial Dysfunction Induced by Lithium via Maintenance of Mitochondrial Function, Inhibition of Oxidative Stress, and Mitochondrial Swelling in Rat Heart-Isolated Mitochondria.","authors":"Mir-Jamal Hosseini, Milad Hossein Zadeh, Mohammad Shabani, Vahed Adhami, Hanieh Delavari, Ahmad Salimi","doi":"10.1007/s12012-025-10060-0","DOIUrl":"10.1007/s12012-025-10060-0","url":null,"abstract":"Due to environmental and medicinal exposures to lithium, as well as its uptake and accumulation in various plant species as human food source, concerns about lithium toxicity and negative impact on different organs especially heart have been raised. The toxicity mechanism of lithium is still unclear, but it has been suggested that some its harmful effects may be related to mitochondrial dysfunction and oxidative stress. Previous studies have demonstrated that plant-derived natural compounds can ameliorate mitochondrial dysfunction induced by various chemicals. In the current study, we examined the effects of vanillic acid as a plant-derived natural compound on lithium-stimulated mitochondrial dysfunction in rat heart-isolated mitochondria and its potential mechanisms of attenuating damages to improve function of mitochondria during 60 min. Mitochondrial injury in rat heart-isolated mitochondria was induced by lithium (125 µM, according to previous studies) and portative effect of vanillic acid (10, 50, and 100 µM) was assessed using mitochondrial toxicity parameters such as the functional state of mitochondria, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, mitochondrial swelling, and malondialdehyde (MDA) levels. Our results confirmed that vanillic acid (10, 50, and 100 µM) significantly mitigated mitochondrial dysfunction triggered by lithium, evidenced by the decline in formation of ROS and MDA, improvement the mitochondrial membrane potential, inhibition of mitochondrial swelling, and the increase of the functional state of mitochondria. Our findings suggested that vanillic acid mitigated mitochondrial dysfunction via maintenance of mitochondrial function, inhibition of oxidative stress and mitochondrial swelling, it could be developed as mitochondrial protective agents in the prevention of cardiotoxicity induced by lithium.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1780-1790"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0