Cardiovascular Toxicology最新文献

An Integrated Network Pharmacology and RNA-seq Approach for Exploring the Protective Effect of Isoquercitrin in Doxorubicin-Induced Cardiotoxicity: Identification of Novel Genes.

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-18 DOI: 10.1007/s12012-025-09968-4

Habib Alam, Wei Bailing, Feng Zhao, Hayan Ullah, Inam Ullah, Muhsin Ali, Ijaz Ullah, Reyisha Tuerhong, Luying Zhang, Lei Shi

{"title":"An Integrated Network Pharmacology and RNA-seq Approach for Exploring the Protective Effect of Isoquercitrin in Doxorubicin-Induced Cardiotoxicity: Identification of Novel Genes.","authors":"Habib Alam, Wei Bailing, Feng Zhao, Hayan Ullah, Inam Ullah, Muhsin Ali, Ijaz Ullah, Reyisha Tuerhong, Luying Zhang, Lei Shi","doi":"10.1007/s12012-025-09968-4","DOIUrl":"https://doi.org/10.1007/s12012-025-09968-4","url":null,"abstract":"Cardiotoxicity, a severe side effect of cytotoxic drugs like doxorubicin (DOX), can lead to cardiomyopathy and heart failure, significantly impacting patient prognosis. This study investigates the molecular mechanisms of DOX-induced cardiotoxicity and explores isoquercitrin (IQC) as a potential therapeutic agent. RNA-sequencing analysis revealed 7855 dysregulated genes in DOX vs. Control and 3853 in DOX + IQC vs. DOX groups. Functional enrichment analysis of upregulated genes in the DOX vs. Control group highlighted cytokine-cytokine receptor interaction and calcium signaling pathways as significant immune-related KEGG pathways. Immune genes were shortlisted based on inflammatory functions, followed by protein-protein interaction analysis and hub gene identification. This process revealed IL6, IL1B, IL10, CCL19, CD27, CSF1R, ADRB2, GDF15, TNFRSF10B, and PADI4 as the top 10 interacting immune hub genes. Validation in the DOX + IQC vs. DOX group showed that IQC downregulated CCL19, IL10, PADI4, and CSF1R genes. Computational drug design techniques, including virtual screening and molecular dynamic simulations, identified promising targets for IQC. These targets were experimentally validated using RT-qPCR in AC16 cell lines under four conditions: control, DOX, low dose DOX + IQC, and high dose DOX + IQC. The study demonstrates that IQC significantly reduces inflammation and oxidative stress in human AC16 cardiomyocyte cell line by downregulating inflammatory and stress pathways induced by DOX. It concludes that CCL19 and PADI4 are crucial immune biomarkers for treating DOX-induced cardiotoxicity using IQC, providing insights into potential therapeutic strategies using plant-based compounds to mitigate the cardiotoxic effects of DOX in cancer treatment.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439572","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

RNF146 Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating the Ubiquitination-Mediated Degradation of DAPK1 to Inhibit Ferroptosis.

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-14 DOI: 10.1007/s12012-025-09972-8

Xiangdong Qiu, Pengfei Yan, Qingyu Zhao, Lehong Yuan

{"title":"RNF146 Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating the Ubiquitination-Mediated Degradation of DAPK1 to Inhibit Ferroptosis.","authors":"Xiangdong Qiu, Pengfei Yan, Qingyu Zhao, Lehong Yuan","doi":"10.1007/s12012-025-09972-8","DOIUrl":"https://doi.org/10.1007/s12012-025-09972-8","url":null,"abstract":"Ring finger protein 146 (RNF146) participates in regulating ferroptosis and ferroptosis is involved in myocardial ischemia/reperfusion injury (MI/RI). However, the effects and mechanisms of RNF146 in MI/RI are still unclear. TTC, H&E, IHC, DHE stainings, and echocardiography technology were used to determine the myocardial infarction area, pathological injury, level of RNF146, ROS, and cardiac function parameters, respectively. CCK-8 was employed to determine the cell viability. The corresponding kits, RT-qPCR, and western blot were adopted to determine the levels of CK-MB, LDH, Fe2+, MDA, ROS, gene expression levels of RNF146 and death-associated protein kinase 1 (DAPK1), protein expression levels of RNF146, DAPK1, GPX4, FTH1, and ACSL4. Co-immunoprecipitation, cycloheximide tracking, and ubiquitination assays to investigate the relationship between RNF146 and DAPK1. Ferroptosis occurred in mice with MI/RI and inhibiting ferroptosis could alleviate MI/RI. Moreover, the expression of RNF146 is down-regulated in MI/RI, and overexpression of RNF146 can inhibit H/R-induced ferroptosis of cardiomyocytes. Mechanistically, RNF146 promotes ubiquitination and degradation of DAPK1. In addition, the effects of overexpressed RNF146 in alleviating MI/RI were effectively reversed by overexpressing DAPK1. This study demonstrated that RNF146 alleviates MI/RI by facilitating the ubiquitylation-mediated degradation of DAPK1 to reduce ferroptosis.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425151","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

Sigma-1 Receptor Specific Biological Functions, Protective Role, and Therapeutic Potential in Cardiovascular Diseases.

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-12 DOI: 10.1007/s12012-025-09975-5

Ahmed Almaamari, Marwa Sultan, Tao Zhang, Eskandar Qaed, Shang Wu, Ruoqi Qiao, Yuxin Duan, Shanshan Ding, Gang Liu, Suwen Su

引用次数: 0

Famciclovir Ameliorates Platelet Activation and Thrombosis by AhR-Regulated Autophagy.

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-10 DOI: 10.1007/s12012-025-09971-9

Yue Ming, Qilong Zhou, Guang Xin, Zeliang Wei, Chengjie Ji, Kui Yu, Shiyi Li, Boli Zhang, Junhua Zhang, Youping Li, Hongchen He, Wen Huang

{"title":"Famciclovir Ameliorates Platelet Activation and Thrombosis by AhR-Regulated Autophagy.","authors":"Yue Ming, Qilong Zhou, Guang Xin, Zeliang Wei, Chengjie Ji, Kui Yu, Shiyi Li, Boli Zhang, Junhua Zhang, Youping Li, Hongchen He, Wen Huang","doi":"10.1007/s12012-025-09971-9","DOIUrl":"https://doi.org/10.1007/s12012-025-09971-9","url":null,"abstract":"Cardiovascular diseases (CVDs) and their severe complications have posed immense challenges to global healthcare systems. A significant obstacle in this field lies in the development of innovative targets, mechanisms, and drugs to mitigate the side effects associated with current antiplatelet therapies. Through screening relevant CVD targets in the Gene Card database, we found that AhR appears to be linked to CVDs. Computer-aided drug screening and molecular docking techniques identified famciclovir as a potential AhR inhibitor. Further experiments demonstrated that famciclovir suppresses AhR expression and platelet activation in thrombin-stimulated platelets, significantly reducing mitochondrial damage and oxidative stress. Notably, oral administration of famciclovir significantly inhibits thrombin-induced platelet aggregation without affecting coagulation factors or thrombolysis systems. Moreover, famciclovir mitigates FeCl3-induced carotid arterial thrombosis and cerebral thrombosis induced by middle cerebral artery occlusion. Our study suggests that inhibiting AhR expression with famciclovir effectively reduces platelet activation and thrombosis, offering promise as a potential therapeutic strategy for improving CVDs.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381693","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

TRIM21 Promotes Endothelial Cell Activation via Accelerating SOCS3 Ubiquitination Degradation in Atherosclerosis.

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-08 DOI: 10.1007/s12012-025-09965-7

Zhenxuan Hao, Yihuan Wang, Linlin Chen, Yanjun Zhou, Dezhou Fang, Wenxiang Yao, Lili Xiao, Yanzhou Zhang

{"title":"TRIM21 Promotes Endothelial Cell Activation via Accelerating SOCS3 Ubiquitination Degradation in Atherosclerosis.","authors":"Zhenxuan Hao, Yihuan Wang, Linlin Chen, Yanjun Zhou, Dezhou Fang, Wenxiang Yao, Lili Xiao, Yanzhou Zhang","doi":"10.1007/s12012-025-09965-7","DOIUrl":"https://doi.org/10.1007/s12012-025-09965-7","url":null,"abstract":"Activated endothelial cells play an important role in the beginning of atherosclerotic disease by secreting various proteins and inflammatory cytokines. Ubiquitination is one of the most common post-translational changes in cells. However, the role and mechanisms of ubiquitination in endothelial cell activation remain poorly understood. In this study, we identified TRIM21 as an E3 ubiquitin ligase with increased expression in atherosclerotic disease and activated endothelial cells. Knockdown of TRIM21 resulted in reduced secretion of inflammatory factors and attenuated the pyroptosis of endothelial cells, inhibiting the progression of atherosclerosis. Mechanistically, TRIM21 could bind and ubiquitinate SOCS3, thereby enhancing NLRP3-mediated pyroptosis. Taken together, we found that endothelial TRIM21 activated the JAK/STAT3 pathway by degrading SOCS3, which in turn promoted NLRP3-mediated pyroptosis and aggravated atherosclerosis, revealing that TRIM21 may be a promising treatment target for the medical management of atherosclerosis.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373867","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

Association Between Heavy Metals Mixtures and Life's Essential 8 Score in General US Adults.

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-07 DOI: 10.1007/s12012-025-09969-3

Xugang Kong, Chuang Li, Yiwen Pan

{"title":"Association Between Heavy Metals Mixtures and Life's Essential 8 Score in General US Adults.","authors":"Xugang Kong, Chuang Li, Yiwen Pan","doi":"10.1007/s12012-025-09969-3","DOIUrl":"https://doi.org/10.1007/s12012-025-09969-3","url":null,"abstract":"Heavy metals were toxic environmental pollutants capable of entering the human body, posing significant risks to human health. Life's Essential 8 (LE8) score is a new comprehensive index constructed for quantifying cardiovascular health (CVH). However, the association between heavy metals mixtures and LE8 appears ambiguous. To investigated the association between heavy metals and cardiovascular health in US population. Urinary heavy metals concentrations (barium, cadmium, cobalt, manganese, molybdenum, lead, antimony, strontium, thallium, tin, tungsten, uranium, cesium) were Ln-transformed and LE8 was consisted of eight metrics. Single and multivariate linear regression, weighted quantile sum (WQS) and Bayesian kernel machine regression models (BKMR) were utilized to assess the association between single and mixed exposure of thirteen heavy metals concentrations and LE8. In 4339 participants from National Health and Nutrition Examination Survey 2007-2018, single urinary heavy metals barium, cadmium, cobalt, lead, antimony, strontium, tin, tungsten, uranium and cesium showed a significant negative association with LE8. WQS models showed heavy metals mixture was negatively associated with LE8 (β = - 2.720, 95% CI - 3.660, - 1.790). BKMR analysis also demonstrated a downward trend of heavy metals mixture and LE8. Both WQS analyzed weights and the conditional posterior inclusion probabilities (condPIP) of BKMR showed that cadmium (37.78%, condPIP = 1.000), barium (24.56%, condPIP = 0.537) and uranium (14.71%, condPIP = 0.646) contributed most for these negative associations. Single and mixed heavy metals, especially cadmium, barium and uranium were negatively associated with LE8 score, a new comprehensive CVH index, predicting an increasing risk of cardiovascular diseases.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370518","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

Mercury-Mediated Cardiovascular Toxicity: Mechanisms and Remedies. 汞引起的心血管毒性：机制与补救措施

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-04 DOI: 10.1007/s12012-025-09966-6

Arash Amin, Maryam Saadatakhtar, Ahmad Mohajerian, Seyed Mehdi Marashi, Somayeh Zamanifard, Ali Keshavarzian, Parisa Molaee, Mohammad Sadegh Keshmiri, Farahnaz Nikdoust

{"title":"Mercury-Mediated Cardiovascular Toxicity: Mechanisms and Remedies.","authors":"Arash Amin, Maryam Saadatakhtar, Ahmad Mohajerian, Seyed Mehdi Marashi, Somayeh Zamanifard, Ali Keshavarzian, Parisa Molaee, Mohammad Sadegh Keshmiri, Farahnaz Nikdoust","doi":"10.1007/s12012-025-09966-6","DOIUrl":"https://doi.org/10.1007/s12012-025-09966-6","url":null,"abstract":"Mercury is a significant environmental pollutant and public health threat, primarily recognized for its neurotoxic effects. Increasing evidence also highlights its harmful impact on the cardiovascular system, particularly in adults. Exposure to mercury through contaminated soil, air, or water initiates a cascade of pathological events that lead to organ damage, including platelet activation, oxidative stress, enhanced inflammation, and direct injury to critical cells such as cardiomyocytes and endothelial cells. Endothelial activation triggers the upregulation of adhesion molecules, promoting the recruitment of leukocytes and platelets to vascular sites. These interactions activate both platelets and immune cells, creating a pro-inflammatory, prothrombotic environment. A key outcome is the formation of platelet-leukocyte aggregates (PLAs), which exacerbate thromboinflammation and endothelial dysfunction. These processes significantly elevate cardiovascular risks, including thrombosis and vascular inflammation. This study offers a comprehensive analysis of the mechanisms underlying mercury-induced cardiotoxicity, focusing on oxidative stress, inflammation, and cellular dysfunction.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188298","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

Associations Between Lead and Cadmium Exposure and Subclinical Cardiovascular Disease in U.S. Adults.

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-01 Epub Date: 2025-01-28 DOI: 10.1007/s12012-024-09955-1

Lin Liu, Aimin Xu, Bernard M Y Cheung

{"title":"Associations Between Lead and Cadmium Exposure and Subclinical Cardiovascular Disease in U.S. Adults.","authors":"Lin Liu, Aimin Xu, Bernard M Y Cheung","doi":"10.1007/s12012-024-09955-1","DOIUrl":"10.1007/s12012-024-09955-1","url":null,"abstract":"The impact of lead and cadmium exposure on subclinical cardiovascular disease (CVD), indicated by elevated high-sensitivity cardiac troponin (hs-cTnT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) remains uncertain. We analyzed data from participants aged 20 and older, without overt CVD, in the National Health and Nutrition Examination Survey (NHANES; 1999-2004). Elevated lead and cadmium levels were defined as 3.5 μg/dL and 1.0 μg/L (inductively coupled plasma mass spectrometry) and 3.8 μg/dL and 0.9 μg/L (atomic absorption spectrometry), respectively. Elevated hs-cTnT was ≥ 19 ng/L, and elevated NT-proBNP was ≥ 125 pg/mL. Multivariate logistic regression estimated the odds ratios (OR) and 95% confidence intervals (CI) for elevated biomarkers. Among 10,197 participants (mean age 48.8 years; 50.3% female), 5.3% had elevated hs-cTnT and 19.4% had elevated NT-proBNP. Elevated blood lead was associated with increased ORs for elevated hs-cTnT (OR 1.45, 95% CI 1.15-1.84) and NT-proBNP (OR 1.66, 95% CI 1.40-1.97). The corresponding ORs (95% CI) for elevated blood cadmium were 1.33 (1.02, 1.74) and 1.39 (1.18, 1.65). The effect of elevated blood lead on NT-proBNP was particularly pronounced among non-Hispanic Blacks (OR [95% CI], 3.26 [2.24, 4.74]) compared to Mexican Americans (1.46 [0.99, 2.17]) and non-Hispanic Whites (1.31 [1.02, 1.68]) and was stronger in individuals with impaired kidney function (OR [95% CI], 2.31 [1.43, 3.75]) compared to those with normal kidney function (1.44 [1.18, 1.75]). This study first reveals the association between lead and cadmium exposure and subclinical CVD, underscoring the need for targeted preventive measures to reduce cardiovascular risk and improve health outcomes.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"282-293"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051632","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

A Meta-analysis of the Risk of Adverse Cardiovascular Events in Patients with Cancer Treated with Inhibitors of the PI3K/AKT/mTOR Signaling Pathway. 使用 PI3K/AKT/mTOR 信号通路抑制剂的癌症患者发生不良心血管事件风险的 Meta 分析。

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-09 DOI: 10.1007/s12012-024-09933-7

Xiao Liang, Chengrong Zhang, Yuyao Tang, YongXin Li, Zijun Zhu, Tianlei Qiu, Jiuda Zhao

{"title":"A Meta-analysis of the Risk of Adverse Cardiovascular Events in Patients with Cancer Treated with Inhibitors of the PI3K/AKT/mTOR Signaling Pathway.","authors":"Xiao Liang, Chengrong Zhang, Yuyao Tang, YongXin Li, Zijun Zhu, Tianlei Qiu, Jiuda Zhao","doi":"10.1007/s12012-024-09933-7","DOIUrl":"10.1007/s12012-024-09933-7","url":null,"abstract":"With the increasing of PI3K/AKT/mTOR (PAM) inhibitors in cancer therapy, there is a growing need to understand the incidence of cardiovascular events (CVAEs) associated with PAM inhibitors. A systematic search of all randomized clinical trials (RCTs) containing at least one PAM group in electronic databases such as PubMed, ClinicalTrials.gov registry, Embase, Medline, Cochrane Library, and major conferences was performed to extract available CVAEs. The cut-off date was January 31, 2024. Study heterogeneity was assessed using the I2 statistic. The risk of CVAEs associated with PAM inhibitors was calculated using Peto OR. The primary outcome was the incidence (95% CI) of PAM inhibitors cardiovascular adverse events in the total population and subgroups. The secondary outcome was the pooled risk of different CVAEs associated with PAM inhibitor exposure in the RCTs. 33 unique RCTs (n = 12,351) were included. The incidence of PAM inhibitors CVAEs of any grade in the intervention group was 48.2%, yielding a combined OR of 2.52 (95% CI 1.82-3.49). The incidence of severe adverse cardiovascular events (≥ grade 3) in the intervention group was estimated at 7.1%, yielding a combined Peto OR of 1.41 (95% CI 1.04-1.93). PAM inhibitors were associated with an increased risk of 5 CVAEs including peripheral edema, lymphoedema, hypercholesterolemia, hypertriglyceridaemia and hyperlipidemia, with higher risks for hypercholesterolemia (Peto OR: 3.27,95% CI 2.61-4.11, P < 0.01; I2 = 55.5%, P = 0.06) and hyperlipidemia (Peto OR: 3.53. 95% CI 1.70-7.32, P < 0.01; I2 = 19.3%, P = 0.29). This study identified an overall incidence of PAM inhibitors CVAEs and the increased risks associated with PAM inhibitor for five specific CVAEs, not confined to hypercholesterolemia and peripheral edema.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"269-281"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615304","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

Cardiotoxicity Associated With a Low Doses of 5-FU Promotes Morphoquantitative Changes in the Intrinsic Cardiac Nervous System. 低剂量 5-FU 引起的心脏毒性会促进心脏内在神经系统的形态定量变化

IF 3.4 3区医学

Cardiovascular Toxicology Pub Date : 2025-02-01 Epub Date: 2025-01-26 DOI: 10.1007/s12012-024-09958-y

Karile Cristina da Costa Salomão, Mariana Conceição da Silva, Lilian Catarim Fabiano, Pedro Luiz Zonta de Freitas, Camila Quaglio Neves, Stephanie Carvalho Borges, Ana Cristina Breithaupt-Faloppa, Carmem Patrícia Barbosa, Nilza Cristina Buttow

{"title":"Cardiotoxicity Associated With a Low Doses of 5-FU Promotes Morphoquantitative Changes in the Intrinsic Cardiac Nervous System.","authors":"Karile Cristina da Costa Salomão, Mariana Conceição da Silva, Lilian Catarim Fabiano, Pedro Luiz Zonta de Freitas, Camila Quaglio Neves, Stephanie Carvalho Borges, Ana Cristina Breithaupt-Faloppa, Carmem Patrícia Barbosa, Nilza Cristina Buttow","doi":"10.1007/s12012-024-09958-y","DOIUrl":"10.1007/s12012-024-09958-y","url":null,"abstract":"5-Fluorouracil (5-FU) is a chemotherapeutic that is used to treat solid tumors. However, 5-FU is associated with several side effects, including cardiotoxicity. Considering the importance of the intrinsic cardiac nervous system (ICNS) for the heart and that little is known about effects of 5-FU on this nervous system plexus, the purpose of the present study was to evaluate effects 5-FU at a low dose on the ICNS and oxidative and inflammatory effects in the heart in Wistar rats. The rats were divided into two groups: treated and 5-FU (n = 6/group). The control group received saline only. The treated group received the following clinical doses of 5-FU: 15 mg/kg for 4 consecutive days, followed by 6 mg/kg for 4 days alternated with non-treatment days, and finally 15 mg/kg as the last dose on day 14. On day 15, the rats were euthanized and underwent thoracotomy. The atria were used for histological analysis, and the ventricles were used for biochemical analysis. The results showed an increase in neuronal density and a decrease in ganglionic and neuronal area in the ICNS. Furthermore, tissue inflammation was observed, indicated by an increase in proinflammatory factors and the enzymatic activity of myeloperoxidase and n-acetyl-glucosaminidase. Oxidative stress was also observed, confirmed by a reduction of endogenous antioxidant defenses and the presence of lipoperoxidation. Treatment with 5-FU also caused cardiac atrophy and fibrosis. These findings indicate that cardiotoxicity is present with 5-FU treatment and affects the morphometric aspects of the ICNS.","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"193-204"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037228","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