RESUMO
Many studies have shown the negative relationship between long term exposure to PM2.5 and cardiac dysfunction. Recently, studies have shown that even a single exposure of PM2.5 from air sample in permissible range can induce very mild cardiac pathological changes. In the present study, we revisited the toxic effect of PM2.5 on rat heart by adopting single and multiple exposure durations. Female Wistar rats were exposed to PM2.5 at a concentration of 250 µg/m3 daily for 3 hr for single (1 day) and multiple (7, 14, 21 days) durations. The major pathological changes noted in 21 days exposed myocardium comprised of an elevated ST segment (the segment between the S wave and the T wave), development of cardiac fibrosis, hypertrophy, cardiac injury, tissue inflammation and declined cardiac function. With 14 days exposed heart, the electrocardiograms (ECG),data showed insignificantly declined heart rate and an increased QT (the time from the start of the Q wave to the end of the T wave) interval along with mild fibrosis, hypertrophy and lesser number of TUNEL positive cells. On the other hand, single- and 7-days exposure to PM2.5 did not impart any significant changes in the myocardium. To determine the reversibility potential of PM2.5 induced cardiotoxicity, a washout period of 24 hours was adopted and all observed changes in the myocardium were reversed till day 7, but not in 14- and 21-days exposed samples. Based on the above findings we concluded that PM2.5 associated cardiac dysfunction is the cumulative outcome of ineffective cardiac adaptive and repair process that accumulate additively over the time due to prolonged exposure durations.
Assuntos
Poluentes Atmosféricos , Coração , Material Particulado , Ratos Wistar , Animais , Material Particulado/toxicidade , Material Particulado/análise , Ratos , Feminino , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Coração/efeitos dos fármacos , Miocárdio/patologiaRESUMO
S-Limonene (s-Lim) is a monocyclic monoterpene found in a variety of plants and has been shown to present antioxidant and cardioprotective activity in experimental models of myocardial infarction. The aim of this study was to evaluate the potential mechanism by which s-Lim exerts its antiarrhythmic effect, focusing on the blockade of ß-adrenoceptor (ß-AR) and its effects on various in vivo and in vitro parameters, including electrocardiogram (ECG) measurements, left ventricular developed pressure (LVDP), the ß-adrenergic pathway, sarcomeric shortening and L-type calcium current (ICa,L). In isolated hearts, 10 µM of s-Lim did not alter the ECG profile or LVPD. s-Lim increased the heart rate corrected QT interval (QTc) (10.8%) at 50 µM and reduced heart rate at the concentrations of 30 (12.4%) and 50 µM (16.6%). s-Lim (10 µM) also inhibited the adrenergic response evoked by isoproterenol (ISO) (1 µM) reducing the increased of heart rate, LVDP and ECG changes. In ventricular cardiomyocyte, s-Lim antagonized the effect of dobutamine by preventing the increase of sarcomeric shortening, demonstrating a similar effect to atenolol (blocker ß1-AR). In vivo, s-Lim antagonized the effect of ISO (agonists ß1-AR), presenting a similar effect to propranolol (a non-selective blocker ß-AR). In ventricular cardiomyocyte, s-Lim did not alter the voltage dependence for ICa,L activation or the ICa,L density. In addition, s-Lim did not affect changes in the ECG effect mediated by 5 µM forskolin (an activator of adenylate cyclase). In an in vivo caffeine/ISO-induced arrhythmia model, s-Lim (1 mg/kg) presented antiarrhythmic action verified by a reduced arrhythmia score, heart rate, and occurrence of ventricular premature beats and inappropriate sinus tachycardia. These findings indicate that the antiarrhythmic activity of s-Lim is related to blockade of ß-AR in the heart.
Assuntos
Antiarrítmicos , Limoneno , Ratos Wistar , Receptores Adrenérgicos beta , Transdução de Sinais , Animais , Ratos , Antiarrítmicos/farmacologia , Masculino , Receptores Adrenérgicos beta/metabolismo , Limoneno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Terpenos/farmacologia , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Cicloexenos/farmacologia , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , Isoproterenol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismoRESUMO
Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction. Transcriptomic analysis identifies nine critical signaling pathways related to cellular fate transitions, leading to the evaluation of seventeen modulators for their therapeutic potential in a mini-repair model. A scoring system quantitatively evaluates the restoration of abnormal electrophysiology, demonstrating that the phased combination of TGFß inhibitor SB431542, Rho kinase inhibitor Y27632, and WNT activator CHIR99021 yields enhanced functional restoration compared to single factor treatments in both engineered and mouse myocardial infarction model. This engineered heart tissue repair model effectively captures the phased remodeling following myocardial infarction, providing a crucial platform for discovering therapeutic targets for ischemic heart disease.
Assuntos
Dioxóis , Fibrose , Infarto do Miocárdio , Piridinas , Engenharia Tecidual , Animais , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Camundongos , Humanos , Piridinas/farmacologia , Piridinas/uso terapêutico , Engenharia Tecidual/métodos , Dioxóis/farmacologia , Dioxóis/uso terapêutico , Miocárdio/patologia , Miocárdio/metabolismo , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Modelos Animais de Doenças , Transdução de Sinais , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Remodelação Ventricular/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Coração/fisiopatologia , Coração/efeitos dos fármacos , AmidasRESUMO
BACKGROUND: Exposure to phenols has been linked in animal models and human populations to cardiac function alterations and cardiovascular diseases, although their effects on cardiac electrical properties in humans remains to be established. This study aimed to identify changes in electrocardiographic (ECG) parameters associated with environmental phenol exposure in adults of a midwestern large cohort known as the Fernald Community Cohort (FCC). METHODS: During the day of the first comprehensive medical examination, urine samples were obtained, and electrocardiograms were recorded. Cross-sectional linear regression analyses were performed. RESULTS: Bisphenol A (BPA) and bisphenol F (BPF) were both associated with a longer PR interval, an indication of delayed atrial-to-ventricle conduction, in females (p < 0.05) but not males. BPA combined with BPF was associated with an increase QRS duration, an indication of delayed ventricular activation, in females (P < 0.05) but not males. Higher triclocarban (TCC) level was associated with longer QTc interval, an indication of delayed ventricular repolarization, in males (P < 0.01) but not females. Body mass index (BMI) was associated with a significant increase in PR and QTc intervals and ventricular rate in females and in ventricular rate in males. In females, the combined effect of being in the top tertile for both BPA urinary concentration and BMI was an estimate of a 10% increase in PR interval. No associations were found with the other phenols. CONCLUSION: Higher exposure to some phenols was associated with alterations of cardiac electrical properties in a sex specific manner in the Fernald cohort. Our population-based findings correlate directly with clinically relevant parameters that are associated with known pathophysiologic cardiac conditions in humans.
Assuntos
Eletrocardiografia , Fenóis , Humanos , Feminino , Masculino , Fenóis/urina , Pessoa de Meia-Idade , Adulto , Estudos Transversais , Estudos de Coortes , Exposição Ambiental/análise , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/urina , Idoso , Coração/efeitos dos fármacosRESUMO
Oxidative stress occurs during ex-situ heart perfusion (ESHP) and may negatively affect functional preservation of the heart. We sought to assess the status of key antioxidant enzymes during ESHP, and the effects of augmenting these antioxidants on the attenuation of oxidative stress and improvement of myocardial and endothelial preservation in ESHP. Porcine hearts were perfused for 6 hours with oxygen-derived free-radical scavengers polyethylene glycol (PEG)-catalase or PEG-superoxide dismutase (SOD) or with naive perfusate (control). The oxidative stress-related modifications were determined in the myocardium and coronary vasculature, and contractile function, injury, and endothelial integrity were compared between the groups. The activity of key antioxidant enzymes decreased and adding catalase and SOD restored the enzyme activity. Cardiac function and endothelial integrity were preserved better with restored catalase activity. Catalase and SOD both decreased myocardial injury and catalase reduced ROS production and oxidative modification of proteins in the myocardium and coronary vasculature. The activity of antioxidant enzymes decrease in ESHP. Catalase may improve the preservation of cardiac function and endothelial integrity during ESHP. While catalase and SOD may both exert cardioprotective effects, unbalanced SOD and catalase activity may paradoxically increase the production of reactive species during ESHP.
Assuntos
Catalase , Sequestradores de Radicais Livres , Estresse Oxidativo , Superóxido Dismutase , Animais , Suínos , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Sequestradores de Radicais Livres/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Perfusão/métodos , Miocárdio/metabolismo , Polietilenoglicóis/farmacologia , Coração/fisiologia , Coração/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Preservação de Órgãos/métodosRESUMO
Cardiovascular disease (CVD) represents a significant global health challenge, remaining the leading cause of illness and mortality worldwide. The adult heart's limited regenerative capacity poses a major obstacle in repairing extensive damage caused by conditions like myocardial infarction. In response to these challenges, nanomedicine has emerged as a promising field aimed at improving treatment outcomes through innovative drug delivery strategies. Nanocarriers, such as nanoparticles (NPs), offer a revolutionary approach by facilitating targeted delivery of therapeutic agents directly to the heart. This precise delivery system holds immense potential for treating various cardiac conditions by addressing underlying mechanisms such as inflammation, oxidative stress, cell death, extracellular matrix remodeling, prosurvival signaling, and angiogenic pathways associated with ischemia-reperfusion injury. In this review, we provide a concise summary of the fundamental mechanisms involved in cardiac remodeling and regeneration. We explore how nanoparticle-based drug delivery systems can effectively target the afore-mentioned mechanisms. Furthermore, we discuss clinical trials that have utilized nanoparticle-based drug delivery systems specifically designed for cardiac applications. These trials demonstrate the potential of nanomedicine in clinical settings, paving the way for future advancements in cardiac therapeutics through precise and efficient drug delivery. Overall, nanomedicine holds promise in revolutionizing the treatment landscape of cardiovascular diseases by offering targeted and effective therapeutic strategies that address the complex pathophysiology of cardiac injuries.
Assuntos
Nanomedicina , Medicina Regenerativa , Humanos , Medicina Regenerativa/métodos , Nanomedicina/métodos , Animais , Nanopartículas , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/terapia , Sistemas de Liberação de Medicamentos/métodos , Regeneração/efeitos dos fármacos , Coração/efeitos dos fármacos , Coração/fisiologiaRESUMO
Objective: The aim of the study was to evaluate the effect of dipeptidyl peptidase-4 inhibitors (DPP4i) on cardiac structure and function by cardiac magnetic resonance (CMR). Research Methods & Procedures: Database including PubMed, Cochrane library, Embase and SinoMed for clinical studies of DPP4i on cardiac structure and function by CMR were searched. Two authors extracted the data and evaluated study quality independently. Mean difference (MD) or standardized MD and 95% confidence intervals (CI) were used for continuous variables. Review Manager 5.3 was used to performed the analysis. Results: Ten references (nine studies) were included in this meta-analysis. Most of the studies were assessed as well quality by the assessment of methodological quality. For clinical control studies, the merged MD values of â³LVEF by fixed-effect model and the pooled effect size in favor of DPP4i was 1.55 (95% CI 0.35 to 2.74, P=0.01). Compared with positive control drugs, DPP4i can significantly improve the LVEF (MD=4.69, 95%CI=2.70 to 6.69), but no such change compared to placebo (MD=-0.20, 95%CI=-1.69 to 1.29). For single-arm studies and partial clinical control studies that reported LVEF values before and after DPP4i treatment, random-effect model was used to combine effect size due to a large heterogeneity (Chi2 = 11.26, P=0.02, I2 = 64%), and the pooled effect size in favor of DPP4i was 2.31 (95% CI 0.01 to 4.62, P=0.05). DPP4i significantly increased the Peak filling rate (PFR) without heterogeneity when the effect sizes of two single-arm studies were combined (MD=31.98, 95% CI 13.69 to 50.27, P=0.0006; heterogeneity test: Chi2 = 0.56, P=0.46, I2 = 0%). Conclusions: In summary, a possible benefit of DPP4i in cardiac function (as measured by CMR) was found, both including ventricular systolic function and diastolic function.
Assuntos
Inibidores da Dipeptidil Peptidase IV , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Humanos , Imageamento por Ressonância Magnética/métodos , Coração/efeitos dos fármacos , Coração/diagnóstico por imagem , Estudos Clínicos como Assunto , Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
Ophidism is a public health problem in tropical countries, occurring predominantly in rural areas. In Colombia, among the species responsible for snakebite envenomation, inflicting high mortality, is the Chocoan bushmaster, Lachesis acrochorda, better known locally by the names "verrugosa (warty)" and "pudridora (rot-causing)". In this research, the cardiotoxic effect of the venom of L. acrochorda in male Wistar rats weighing 230 ± 20 g was evaluated. A statistical design of randomized blocks was implemented with three treated groups, injected with lyophilized venom (doses of 3.22 µg/g, 6.43 µg/g, 12.86 µg/g), and a control group injected with 0.9% saline solution. Electrocardiographic (ECG) recordings were taken from the anesthetized animals, revealing an increase in the amplitude of the P and T waves and an increase in the duration of the QT intervals in the electrocardiographic recordings. These increases were not observed in the control biomodels. In the analysis of the CK and CK-MB enzyme levels, increases were also observed in the levels of cardiac isoenzymes in the injected animals, but none in the control animals. The histopathological analyses carried out reveal that the injected animals showed effects such as interfibrillar and perivascular edema, cellular shortening of the cardiomyocytes, foci with tissue destructuring, and necrosis with contraction bands. In conclusion, the venom of the Lachesis acrochorda snake increases the P and T waves and the QT interval and increases the CK and CK-MB enzymes in the blood. Additionally, it causes interfibrillar and perivascular edema in the cardiac tissue, cardiocytolysis, and contraction bands.
Assuntos
Ratos Wistar , Viperidae , Animais , Masculino , Eletrocardiografia , Coração/efeitos dos fármacos , Ratos , Creatina Quinase Forma MB/sangue , Venenos de Víboras/toxicidade , Creatina Quinase/sangue , Miocárdio/patologia , Frequência Cardíaca/efeitos dos fármacosRESUMO
Introduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood. Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h. Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish. Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.
Assuntos
Adesões Focais , Coração , Nanopartículas Metálicas , Prata , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/química , Coração/efeitos dos fármacos , Coração/embriologia , Prata/toxicidade , Prata/química , Adesões Focais/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Background: Iodinated contrast is commonly used for radiological procedures, with one dose delivering several hundred-fold the daily requirements needed for normal thyroid hormone production. Risks of excess iodine include incident thyroid dysfunction, which is associated with adverse cardiac outcomes, yet there are no prospective studies investigating the changes in cardiac physiology following iodine contrast administration. This study was conducted to investigate the longitudinal relationships between the amount of iodinated contrast administration and changes in cardiac electrophysiology and structure. Methods: A longitudinal cohort study was conducted with prospectively enrolled participants who received iodine contrast for elective computed tomography or coronary angiography. Serum thyroid function tests, electrocardiograms (EKG), and transthoracic echocardiograms were obtained serially until 36 months. Trends of electrical and structural cardiac changes following iodine contrast administration were assessed using mixed effect models. Results: The cohort was composed of 129 patients (median age, 70 [interquartile range: 63, 75] years; 98% male). Larger amounts of iodine exposure were associated with increases in QRS and QTc durations and decreased ejection fraction (EF), and these associations were still observed for follow-up EF after additionally adjusting for baseline values (the high-iodine contrast group vs. the low-iodine contrast group, -4.23% [confidence interval, -7.66% to -0.79%]). Dose-response analyses also showed lower EF with larger amounts of iodine received; these trends were not significant for the EKG parameters studied. Conclusions: Over a period of up to 36 months, a larger amount of administered iodine contrast was associated with lower EF among participants. Further investigation is needed to elucidate the long-term trends of electrical and structural cardiac function after iodine contrast administration.
Assuntos
Meios de Contraste , Ecocardiografia , Eletrocardiografia , Coração , Iodo , Humanos , Meios de Contraste/efeitos adversos , Meios de Contraste/administração & dosagem , Masculino , Feminino , Estudos Longitudinais , Pessoa de Meia-Idade , Idoso , Iodo/efeitos adversos , Iodo/administração & dosagem , Coração/efeitos dos fármacos , Coração/diagnóstico por imagem , Angiografia Coronária , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Testes de Função Tireóidea , Volume Sistólico/efeitos dos fármacosRESUMO
BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) for locally-advanced non-small cell lung cancer (LA-NSCLC) has undergone advances, including increased overall survival (OS) when combined with immune checkpoint blockade (ICB), and using cardiac-sparing techniques to reduce the radiotoxicity. This research investigated 1) how radiotherapy schedules can be optimised with CRT-ICB schemes, and 2) how cardiac-sparing might change the OS for concurrent CRT (cCRT). METHODS AND MATERIALS: Survival data and dosimetric indices were sourced from published studies, with 2-year OS standardised and the hazard ratio of mean heart dose (MHD) against radiotoxicity tabulated in purpose. A published CRT dose-response model was selected, then modified with ICB and cardiac-sparing hypotheses. Models were maximum likelihood fitted, then visualised the prediction outcomes after bootstrapping. RESULTS: The modelled 2-year OS rate of cCRT-ICB reached 71 % (95 % confidence intervals, CI 62 %, 84 %) and 66 % (95 % CI: 53 %, 81 %) for stage IIIA and IIIB/C, respectively, given 60 Gy in 2 Gy-per-fraction. 60 Gy in 30 fractions remained the best schedule for cCRT-ICB, whereas modest dose de-escalation to 55 Gy only reduced the OS in 2 %. Sequential CRT (sCRT)-ICB provided 6 % OS increases versus the best OS rate achieved by sCRT alone. Photon MHD-sparing achieved a 5-10 % increase in modelled 2-year OS, with protons providing a further roughly 5-10 % increase. CONCLUSION: Neither dose-escalation nor de-escalation relative to 60 Gy in 30 fractions influenced the survival with cCRT-ICB, while 5 Gy dose de-escalation might benefit patients with heavily irradiated organs at risk. Cardiac-sparing improved OS, and protons provided advantages for tumours anatomically overlapped or lay below the heart.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Neoplasias Pulmonares , Humanos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Relação Dose-Resposta à Radiação , Coração/efeitos da radiação , Coração/efeitos dos fármacos , Dosagem Radioterapêutica , Órgãos em Risco/efeitos da radiação , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Cardiotoxicidade/etiologia , Imunoterapia/métodos , Masculino , Feminino , Taxa de SobrevidaRESUMO
Bisphenol A (BPA) is a commonly used plastic additive. Since BPA has been banned in maternal and infant food containers in many countries, BPA substitutes have been widely introduced to replace it. By systematically assessing the potential developmental toxicity of BPA substitutes, we observed that the 41-150 nM in vivo BPC exposure (around the reported concentration detected in infant urine: 6-186 nM) induced cardiac defects in zebrafish. Mechanistically, BPC disrupted m6A homeostasis by downregulation of the key m6A methyltransferase, Mettl3, thereby causing the m6A reader, Igf2bp2b, to fail in recognizing and stabilizing the inefficiently m6A-modified acox1 and tnnt2d mRNA. Then, downregulation of Acox1 (a regulator in cardiac fatty acid metabolism) and Tnnt2d (a component of cardiac troponin for muscle contraction) led to cardiac defects. Indeed, the dual cardiac functional axes regulated by the same m6A reader in response to BPC provided new insight into the regulatory mechanisms of epitranscriptomics and cardiac development. Collectively, our study not only presented evidence showing that the internal exposure levels of BPC in humans could lead to cardiac developmental defects but also demonstrated the underlying mechanism of BPC-mediated defects by disrupting the Mettl3-m6A-Igf2bp2b-Acox1/Tnnt2d pathways, which provided potential molecular markers associated with BPC exposure.
Assuntos
Homeostase , Peixe-Zebra , Animais , Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Coração/efeitos dos fármacosRESUMO
Envenomation by reptile venom, particularly from lizards, poses significant health risks and can lead to physiological and cardiovascular changes. The venom of Heloderma horridum horridum, endemic to Colima, Mexico, was tested on Wistar rats. Electrocardiographic (ECG) data were collected pre-treatment and at 5-min intervals for 1 h post-envenomation. A specially designed computational linear regression algorithm (LRA) was used for the segmentation analysis of the ECG data to improve the detection of fiducial points (P, Q, R, S, and T) in ECG waves. Additionally, heart tissue was analyzed for macroscopic and microscopic changes. The results revealed significant electrocardiographic alterations, including pacemaker migration, junctional extrasystoles, and intraventricular conduction aberrations. By applying a linear regression algorithm, the study compensated for noise and anomalies in the isoelectric line in an ECG signal, improving the detection of P and T waves and the QRS complex with an efficiency of 97.5%. Cardiac enzyme evaluation indicated no statistically significant differences between the control and experimental groups. Macroscopic and microscopic examination revealed no apparent signs of damage or inflammatory responses in heart tissues. This study enhances our understanding of the cardiovascular impact of Heloderma venom, suggesting a greater influence on changes in conduction and arrhythmias than on direct cardiac damage to the myocardium.
Assuntos
Algoritmos , Eletrocardiografia , Ratos Wistar , Animais , Ratos , Modelos Lineares , Coração/efeitos dos fármacos , Lagartos , Masculino , Peçonhas/toxicidade , México , Animais PeçonhentosRESUMO
The current study aimed to explore the genotoxic impacts of the insecticide acetamiprid (ACP) on the myocardium and assess the ameliorative role of resveratrol (RSV). Male rats (10/group) were treated via oral route for 90 days: control; ACP (25â¯mg/kg); RSV (20â¯mg/kg); ACP+RSV. Peripheral blood micronucleus test, oxidative stress analysis, comet assay, 8-hydroxydeoxyguanosine and gene expression assessment were performed. The findings revealed that ACP has myocardial genotoxic effects, as demonstrated by increased micronucleus and 8-hydroxydeoxyguanosine formation and increased all comet parameters. Oxidative stress analysis demonstrated that ACP elevated H2O2 and NO levels while decreasing catalase and GST activities. Acetamiprid dysregulated the expression of genes related to oxidative stress and DNA damage response. However, RSV co-treatment resulted in significant protection against these genotoxic impacts. Resveratrol reduced DNA damage and restored the oxidative balance in the myocardium. Moreover, RSV modulated the Nrf2/HO-1 and Atm/P53 pathways, potentiating antioxidant defense and DNA repair.
Assuntos
Antioxidantes , Dano ao DNA , Inseticidas , Miocárdio , Neonicotinoides , Estresse Oxidativo , Resveratrol , Animais , Resveratrol/farmacologia , Masculino , Neonicotinoides/toxicidade , Dano ao DNA/efeitos dos fármacos , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Inseticidas/toxicidade , Testes para Micronúcleos , Ratos Wistar , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Ratos , Ensaio Cometa , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Coração/efeitos dos fármacosRESUMO
Leptin, acting centrally or peripherally, has complex effects on cardiac remodeling and heart function. We previously reported that central leptin exerts an anti-hypertrophic effect in the heart via cardiac PPARß/δ activation. Here, we assessed the impact of central leptin administration and PPARß/δ inhibition on cardiac function. Various cardiac properties, including QRS duration, R wave amplitude, heart rate (HR), ejection fraction (EF), end-diastolic left ventricular mass (EDLVM), end-diastolic volume (EDV), and cardiac output (CO) were analyzed. Central leptin infusion increased cardiac PPARß/δ protein content and decreased HR, QRS duration, and R wave amplitude. These changes induced by central leptin suggested a decrease in the ventricular wall growth, which was confirmed by MRI. In fact, the EDLVM was reduced by central leptin while increased in rats co-treated with leptin and GSK0660, a selective antagonist of PPARß/δ activity. In summary, central leptin plays a dual role in cardiac health, potentially leading to ventricular atrophy and improving heart function when PPARß/δ signaling is intact. The protective effects of leptin are lost by PPARß/δ inhibition, underscoring the importance of this pathway. These findings highlight the therapeutic potential of targeting leptin and PPARß/δ pathways to combat cardiac alterations and heart failure, particularly in the context of obesity.
Assuntos
Leptina , PPAR delta , PPAR beta , Animais , Leptina/farmacologia , Leptina/metabolismo , PPAR beta/metabolismo , PPAR beta/agonistas , PPAR delta/metabolismo , PPAR delta/agonistas , Ratos , Masculino , Coração/efeitos dos fármacos , Ratos Wistar , Atrofia , Frequência Cardíaca/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Sulfonas , TiofenosRESUMO
Manganese (Mn2+) is an abundant chemical element in the earth's crust and is present in soil, water, and industrial environments, including mining, welding, and battery manufacturing. Manganese (Mn) is an essential metal needed as a cofactor for many enzymes to maintain proper biological functions. Excessive exposure to Mn in high doses can result in a condition known as manganism, which results in disorders of the neurological, cardiac, and pulmonary systems. The aim of this study was to assess cardiac susceptibility to manganese intoxication in Colossoma macropomum subjected to a fixed concentration of 4 mg/mL for a period of up to 96 h. This study used 45 Tambaquis (30.38 ± 3.5 g) divided into five groups of 9 animals/treatment. The treated groups were exposed to the manganese concentration for a period of 24, 48, 72, and 96 h, after which the animals' ECGs were recorded, showing heart rate, R-R interval, P-Q interval, QRS complex duration and S-T interval. The results showed that cardiac activity decreased as the contact time increased, with an increase in the P-Q and S-T intervals. This indicates that the breakdown of circulatory homeostasis in these animals was caused by contact time with manganese.
Assuntos
Eletrocardiografia , Manganês , Animais , Manganês/toxicidade , Frequência Cardíaca/efeitos dos fármacos , Intoxicação por Manganês , Coração/efeitos dos fármacos , Coração/fisiologiaRESUMO
The diabetic heart is characterised by functional, morphological and metabolic alterations predisposing it to contractile failure. Chronic sympathetic activation is a feature of the pathogenesis of heart failure, however the type 1 diabetic heart shows desensitisation to ß-adrenergic stimulation. Here, we sought to understand the impact of repeated isoprenaline-mediated ß-stimulation upon cardiac mitochondrial respiratory capacity and substrate metabolism in the 90% pancreatectomy (Px) rat model of type 1 diabetes. We hypothesised these hearts would be relatively protected against the metabolic impact of stress-induced cardiomyopathy. We found that individually both Px and isoprenaline suppressed cardiac mitochondrial respiration, but that this was preserved in Px rats receiving isoprenaline. Px and isoprenaline had contrasting effects on cardiac substrate metabolism, with increased reliance upon cardiac fatty acid oxidation capacity and altered ketone metabolism in the hearts of Px rats, but enhanced capacity for glucose uptake and metabolism in isoprenaline-treated rats. Moreover, Px rats were protected against isoprenaline-induced mortality, whilst isoprenaline elevated cGMP and protected myocardial energetic status in Px rat hearts. Our work suggests that adrenergic stimulation may be protective in the type 1 diabetic heart, and underlines the importance of studying pathological features in combination when modeling complex disease in rodents.
Assuntos
Agonistas Adrenérgicos beta , Isoproterenol , Animais , Agonistas Adrenérgicos beta/farmacologia , Ratos , Masculino , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Diabetes Mellitus Tipo 1/metabolismo , Glucose/metabolismo , Modelos Animais de Doenças , Coração/efeitos dos fármacosRESUMO
BACKGROUND: Metamizole is banned in some countries because of its toxicity, although it is widely used in some European countries. In addition, there is limited information on its safety profile, and it is still debated whether it is toxic to the heart, lungs, liver, kidneys, and stomach. AIMS: Our study investigated the effects of metamizole on the heart, lung, liver, kidney, and stomach tissues of rats. METHODS: Eighteen rats were divided into three groups, wassix healthy (HG), 500 mg/kg metamizole (MT-500), and 1000 mg/kg metamizole (MT-1000). Metamizole was administered orally twice daily for 14 days. Meanwhile, the HG group received pure water orally. Biochemical, histopathologic, and macroscopic examinations were performed on blood samples and tissues. RESULTS: Malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in the lung and gastric tissues of MT-500 and MT-1000 groups were almost the same as those of the HG (p > 0.05). However, MDA levels in the heart and liver tissues of MT-500 and MT-1000 groups were higher (p < 0.05) compared to the HG, while tGSH levels and SOD, and CAT activities were lower (p < 0.05). MDA levels of MT-500 and MT-1000 groups in the kidney tissue increased the most (p < 0.001), and tGSH levels and SOD and CAT activities decreased the most (p < 0.001) compared to HG. Metamizole did not cause oxidative damage in the lung and gastric tissue. While metamizole did not change troponin levels, it significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels compared to HG. Histopathologically, mild damage was detected in heart tissue, moderate damage in liver tissue, and severe damage in renal tissue. However, no histopathologic damage was found in any groups' lung and gastric tissues. CONCLUSION: Metamizole should be used under strict control in patients with cardiac and liver diseases and it would be more appropriate not to use it in patients with renal disease.