scholarly journals Proinflammatory Cytokines Are Soluble Mediators Linked with Ventricular Arrhythmias and Contractile Dysfunction in a Rat Model of Metabolic Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Evaristo Fernández-Sada ◽  
Alejandro Torres-Quintanilla ◽  
Christian Silva-Platas ◽  
Noemí García ◽  
B. Cicero Willis ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Ventricular Arrhythmias ◽  
Mechanical Performance ◽  
Contractile Function ◽  
Ex Vivo ◽  
Heart Function ◽  
Control Group ◽  
Serum Triglycerides ◽  
Rat Cardiomyocytes ◽  
Proinflammatory Mediators

Metabolic syndrome (MS) increases cardiovascular risk and is associated with cardiac dysfunction and arrhythmias, although the precise mechanisms are still under study. Chronic inflammation in MS has emerged as a possible cause of adverse cardiac events. Male Wistar rats fed with 30% sucrose in drinking water and standard chow for 25–27 weeks were compared to a control group. The MS group showed increased weight, visceral fat, blood pressure, and serum triglycerides. The most important increases in serum cytokines included IL-1β(7-fold), TNF-α(84%), IL-6 (41%), and leptin (2-fold), the latter also showing increased gene expression in heart tissue (35-fold). Heart function ex vivo in MS group showed a decreased mechanical performance response to isoproterenol challenge (ISO). Importantly, MS hearts under ISO showed nearly twofold the incidence of ventricular fibrillation. Healthy rat cardiomyocytes exposed to MS group serum displayed impaired contractile function and Ca2+handling during ISO treatment, showing slightly decreased cell shortening and Ca2+transient amplitude (23%), slower cytosolic calcium removal (17%), and more frequent spontaneous Ca2+release events (7.5-fold). As spontaneous Ca2+releases provide a substrate for ventricular arrhythmias, our study highlights the possible role of serum proinflammatory mediators in the development of arrhythmic events during MS.

scholarly journals ASSOCIATION BETWEEN SERUM URIC ACID AND METABOLIC SYNDROME

2018 ◽  
Vol 11 (10) ◽  
pp. 400 ◽  
Author(s):  
Thaslima Nandhini Js ◽  
Savitha Basker G ◽  
Vishnupriya V
Keyword(s):  
Metabolic Syndrome ◽  
Uric Acid ◽  
Venous Blood ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
Serum Triglycerides ◽  
Significant Difference ◽  
Disease Condition ◽  
Student’S T ◽  
Student’S T Test

Objective: Metabolic syndrome is a cluster of disease condition characterized by truncal obesity, hypertriglyceridemia, elevated blood pressure, and insulin resistance. An excessive circulating uric acid (UA) level even within normal range is always comorbid with metabolic syndrome and its components. The aim of the current study was to investigate the association between metabolic syndrome and serum UA level.Methods: A total of 60 subjects were divided into two groups of healthy (30 individuals) and metabolic syndrome patients (30 individuals) from dental outpatient department of Saveetha Dental College and Hospitals. 5 ml of fasting venous blood was collected in the plain collection tubes and centrifuged, and then serum was separated. Then, the serum was used to analyze the fasting blood glucose, serum triglycerides (TGLs), and serum UA by GOD-POD, enzymatic colorimetric, and uricase method, respectively. A statistical analysis was performed using Student’s t-test. p<0.05 was considered to be statistically significant.Result: Mean body mass index (BMI), fasting blood sugar (FBS), TGL, and UA level of control group were 23.36±1.81, 84.45±13.1, 110.9±22.6, and 3.48±1.21 respectively. Mean BMI, FBS, TGL, and UA level of study group were 35.24±3.04, 122.85±23.3, 212.1±39.6 and 9.08±2.63 respectively. There is a significant difference between these two groups with p<0.0001.Conclusion: This study showed that those individuals with metabolic syndrome have higher UA level that indicates hyperuricemia which is a significant predictor of metabolic syndrome.

scholarly journals Standardized Aronia melanocarpa Extract as Novel Supplement against Metabolic Syndrome: A Rat Model

2018 ◽  
Vol 20 (1) ◽  
pp. 6 ◽  
Author(s):  
Vladimir Jakoviljevic ◽  
Petar Milic ◽  
Jovana Bradic ◽  
Jovana Jeremic ◽  
Vladimir Zivkovic ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Dietary Habits ◽  
Ex Vivo ◽  
Heart Function ◽  
Standard Diet ◽  
Oral Supplementation ◽  
Beneficial Effects ◽  
Aronia Melanocarpa ◽  
Dietary Strategies

The aim of our study was to examine the effects of different dietary strategies, high-fat (HFd) or standard diet (Sd) alone or in combination with standardized oral supplementation (0.45 mL/kg/day) of Aronia melanocarpa extract (SAE) in rats with metabolic syndrome (MetS). SAE is an official product of pharmaceutical company Pharmanova (Belgrade, Serbia); however, the procedure for extraction was done by EU-Chem company (Belgrade, Serbia). Rats were divided randomly into six groups: control with Sd, control with Sd and SAE, MetS with HFd, MetS with HFd and SAE, MetS with Sd and MetS with Sd and SAE during 4 weeks. At the end of the 4-week protocol, cardiac function and liver morphology were assessed, while in the blood samples glucose, insulin, iron levels and systemic redox state were determined. Our results demonstrated that SAE had the ability to lower blood pressure and exert benefits on in vivo and ex vivo heart function. Moreover, SAE improved glucose tolerance, attenuated pathological liver alterations and oxidative stress present in MetS. Obtained beneficial effects of SAE were more prominent in combination with changing dietary habits. Promising potential of SAE supplementation alone or in combination with different dietary protocols in triggering cardioprotection should be further examined in future.

scholarly journals ASSESSMENT OF INFLAMMATORY STATUS IN METABOLIC SYNDROME

2018 ◽  
Vol 11 (7) ◽  
pp. 259
Author(s):  
Nivesh Krishna ◽  
Anitha Roy ◽  
Savitha G
Keyword(s):  
Metabolic Syndrome ◽  
Normal Control ◽  
Venous Blood ◽  
Surrogate Marker ◽  
Control Group ◽  
Sample Collection ◽  
Serum Triglycerides ◽  
Inflammatory Status ◽  
Group 2 ◽  
Index Level

Objective: The aim of the present study was to assess the level of inflammation in metabolic syndrome (MetS) individuals by estimating C-reactive protein (CRP) in the individuals.Methods: A total of 60 subjects were selected from those attending the outpatient department of a private hospital and divided into two groups (n=30): Group 1 - healthy individuals and Group 2 - individuals with MetS. Informed consent was obtained from the subjects before sample collection. 5 ml of fasting venous blood was collected and centrifuged at 3000 rpm to separate serum, and then, it was analyzed for fasting blood sugar (FBS) by glucose oxidase-peroxidase method, serum triglycerides (TGL) by colorimetric enzymatic method, and serum CRP by Turbilatex method using ERBA CHEM 5 plus analyzer.Results: Mean body mass index level in control and MetS group is 22.73±2.14 and 35.53±3.57, respectively. Mean FBS levels in the control group and MetS group are 85.6±11.59 and 115.67±24.52, respectively. Mean TGL levels in the normal control group and MetS group are 105.63±30.26 and 181.07±47.76, respectively. Mean CRP levels in the normal control and MetS group are 3.17±1.22 and 8.34±2.48, respectively.Conclusion: CRP level positively correlated with MetS. Evaluation of CRP can be used as a surrogate marker to assess the inflammatory status of MetS individuals.

Co-expression of skeletal and cardiac troponin T decreases mouse cardiac function

2008 ◽  
Vol 294 (1) ◽  
pp. C213-C222 ◽  
Author(s):  
Q.-Q. Huang ◽  
H. Z. Feng ◽  
J. Liu ◽  
J. Du ◽  
L. B. Stull ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Contractile Function ◽  
Troponin T ◽  
Ex Vivo ◽  
Heart Function ◽  
Left Ventricular Pressure ◽  
Experimental System ◽  
Left Ventricular ◽  
Negative Effects

In contrast to skeletal muscles that simultaneously express multiple troponin T (TnT) isoforms, normal adult human cardiac muscle contains a single isoform of cardiac TnT. To understand the significance of myocardial TnT homogeneity, we examined the effect of TnT heterogeneity on heart function. Transgenic mouse hearts overexpressing a fast skeletal muscle TnT together with the endogenous cardiac TnT was investigated in vivo and ex vivo as an experimental system of concurrent presence of two classes of TnT in the adult cardiac muscle.This model of myocardial TnT heterogeneity produced pathogenic phenotypes: echocardiograph imaging detected age-progressive reductions of cardiac function; in vivo left ventricular pressure analysis showed decreased myocardial contractility; ex vivo analysis of isolated working heart preparations confirmed an intrinsic decrease of cardiac function in the absence of neurohumoral influence. The transgenic mice also showed chronic myocardial hypertrophy and degeneration. The dominantly negative effects of introducing a fast TnT into the cardiac thin filaments to produce two classes of Ca2+ regulatory units in the adult myocardium suggest that TnT heterogeneity decreases contractile function by disrupting the synchronized action during ventricular contraction that is normally activated as an electrophysiological syncytium.

scholarly journals Effects of Exercise Intervention on Mitochondrial Stress Biomarkers in Metabolic Syndrome Patients: A Randomized Controlled Trial

2021 ◽  
Vol 18 (5) ◽  
pp. 2242
Author(s):  
Jae Seung Chang ◽  
Jun Namkung
Keyword(s):  
Metabolic Syndrome ◽  
Exercise Training ◽  
Healthy Volunteers ◽  
Stress Responses ◽  
Exercise Intervention ◽  
Controlled Trial ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Serum Triglycerides ◽  
Supervised Exercise

Metabolic syndrome (MetS) pathogenesis involves oxidative stress associated with mitochondrial dysfunction, which triggers integrated stress responses via various compensatory metabolic modulators like mitokines and hepatokines. However, the regulatory mechanisms underlying the exercise-derived benefits with respect to mitokines and hepatokines (potential MetS biomarkers) are unknown. Thus, we investigated the effects of exercise training on MetS biomarkers and their associations with clinical parameters. In this single-center trial, 30 women with MetS were randomly assigned to 12-week supervised exercise or control groups (1:1) and compared with 12 age-matched healthy volunteers. All participants completed the study except one subject in the control group. Expectedly, serum levels of the mitokines, fibroblast growth factor-21 (FGF21), growth differentiation factor-15 (GDF15), and the hepatokine, angiopoietin-like 6 (ANGPTL6), were higher in MetS patients than in healthy volunteers. Moreover, their levels were markedly attenuated in the exercise group. Further, exercise-mediated changes in serum FGF21 and GDF15 correlated with changes in the homeostasis model of assessment of insulin resistance (HOMA-IR) and appendicular lean mass (ALM), respectively. Additionally, changes in serum triglycerides and ANGPTL6 were correlated with changes in leptin. Aberrant mitokine and hepatokine levels can be rectified by relieving metabolic stress burden. Therefore, exercise training may reduce the need for the compensatory upregulation of MetS metabolic modulators by improving gluco-lipid metabolism.

scholarly journals Myocardial performance and adaptive energy pathways in a torpid mammalian hibernator

2015 ◽  
Vol 309 (4) ◽  
pp. R368-R377 ◽  
Author(s):  
Frazer I. Heinis ◽  
Katie L. Vermillion ◽  
Matthew T. Andrews ◽  
Joseph M. Metzger
Keyword(s):  
Contractile Function ◽  
Ex Vivo ◽  
Heart Function ◽  
Systolic Function ◽  
Ischemia Reperfusion ◽  
Ground Squirrels ◽  
Force Frequency ◽  
Atp Production ◽  
Isolated Hearts ◽  
Frequency Relationship

The hearts of mammalian hibernators maintain contractile function in the face of severe environmental stresses during winter heterothermy. To enable survival in torpor, hibernators regulate the expression of numerous genes involved in excitation-contraction coupling, metabolism, and stress response pathways. Understanding the basis of this transition may provide new insights into treatment of human cardiac disease. Few studies have investigated hibernator heart performance during both summer active and winter torpid states, and seasonal comparisons of whole heart function are generally lacking. We investigated the force-frequency relationship and the response to ex vivo ischemia-reperfusion in intact isolated hearts from 13-lined ground squirrels ( Ictidomys tridecemlineatus) in the summer (active, July) and winter (torpid, January). In standard euthermic conditions, we found that winter hearts relaxed more rapidly than summer hearts at low to moderate pacing frequencies, even though systolic function was similar in both seasons. Proteome data support the hypothesis that enhanced Ca2+ handling in winter torpid hearts underlies the increased relaxation rate. Additionally, winter hearts developed significantly less rigor contracture during ischemia than summer hearts, while recovery during reperfusion was similar in hearts between seasons. Winter torpid hearts have an increased glycogen content, which likely reduces development of rigor contracture during the ischemic event due to anaerobic ATP production. These cardioprotective mechanisms are important for the hibernation phenotype and highlight the resistance to hypoxic stress in the hibernator.

scholarly journals 2297 The direct effect of trimethylamine N-oxide (TMAO) on cardiac muscle contractile mechanics

2018 ◽  
Vol 2 (S1) ◽  
pp. 30-30
Author(s):  
Carlee I. Oakley ◽  
David Sanborn ◽  
Nikita Rafie ◽  
Matt Hendrix ◽  
Michael Grillo ◽  
...  
Keyword(s):  
Contractile Function ◽  
Ex Vivo ◽  
Isometric Force ◽  
Isometric Tension ◽  
Right Atrial ◽  
Organ Bath ◽  
Cardiac Contractile Function ◽  
Rat Cardiomyocytes ◽  
Vehicle Treatment ◽  
Beating Frequency

OBJECTIVES/SPECIFIC AIMS: The objective of this study was to determine if trimethylamine N-oxide (TMAO) alone could acutely alter cardiac contractile function on a beat-to-beat basis. METHODS/STUDY POPULATION: CD1 adult mouse hearts were extracted, attached to a force transducer, oxygenated, and paced within an organ bath. Changes in contractility were measured after pipetting or reverse perfusing TMAO through the aorta via a modified Langendorff apparatus to facilitate TMAO delivery into the myocardium. To determine if our findings translated to the human heart, we performed contractility experiments using human right atrial appendage biopsy tissue retrieved during cardiopulmonary bypass procedures. To investigate whether TMAO alters contractile rate, in a separate series of experiments, the atria and sinoatrial node of isolated hearts were kept intact to allow for spontaneous beating without artificial pacing and were treated with TMAO or vehicle. In addition, intracellular calcium measurements were performed on spontaneously beating embryonic rat cardiomyocytes after TMAO or vehicle treatment. RESULTS/ANTICIPATED RESULTS: We found acute exposure to TMAO, diluted into the organ bath, increased average contraction amplitude 20% and 41% at 300 µM and 3000 µM, respectively (p<0.05, n=6). Langendorff reverse perfusion of mouse hearts ex vivo with 300 µM TMAO generated an even greater response than nonperfusion peripheral exposure and increased isometric force 32% (p<0.05, n=3). Consistent with what we observed in mouse hearts, incubation of human atrial muscle tissue with TMAO at 3000 µM increased isometric tension 31% compared with vehicle (p<0.05, n=4). TMAO treatment (3000 µM) also increased average beating frequency of ex vivo mouse hearts by 27% compared with vehicle (p<0.05, n=3) and increased the spontaneous beating frequency of primary rat cardiomyocytes by 13% compared with vehicle treatment (p<0.05, n=4). DISCUSSION/SIGNIFICANCE OF IMPACT: TMAO, at pathological concentrations, directly increases the force and rate of cardiac contractility. Initially, these inotropic and chronotropic effects may be adaptive during CKD; however, chronic increases in isometric tension and beating frequency can promote cardiac remodeling and heart failure. Further translational studies are needed to understand the intricate relationship between the microbiome, kidneys, and heart and to examine if TMAO represents a therapeutic target for reducing cardiovascular mortality in CKD patients.

Attenuated cardiac function degradation in ex vivo pig hearts

2019 ◽  
Vol 43 (3) ◽  
pp. 173-179
Author(s):  
Benjamin Kappler ◽  
Sjoerd van Tuijl ◽  
Bülent Ergin ◽  
Louis Fixsen ◽  
Marco Stijnen ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Ex Vivo ◽  
Heart Function ◽  
Blood Parameters ◽  
Diagnostic Tools ◽  
Control Group ◽  
Isolated Hearts ◽  
Cardiac Hemodynamics ◽  
Cardiac Pump Function

Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, −14.9 ± 6.3%/h vs −9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, −11.8 ± 3.4%/h vs −5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform.

scholarly journals Mitochondrial antioxidant plastomitin alters the myocardial energy state and prevented the development of systolic dysfunction in doxorubicin-induced cardiomyopathy

2020 ◽  
pp. 24-30
Author(s):  
В.Л. Лакомкин ◽  
И.М. Студнева ◽  
А.А. Абрамов ◽  
А.В. Просвирнин ◽  
О.М. Веселова ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Mitochondrial Respiration ◽  
Contractile Function ◽  
Adenine Nucleotide ◽  
Heart Function ◽  
Energy State ◽  
Systolic Dysfunction ◽  
Control Group ◽  
Adenine Nucleotide Pool ◽  
Fractional Shortening

Резюме Цель исследования. Настоящая работа предпринята с целью изучения влияния митохондриального антиоксиданта пластомитина (ПМ, препарат SkQ1) на энергетическое состояние и функцию сердца крыс с кардиомиопатией, вызванной введением доксорубицина (Докс). Материалы и методы. Использовали крыс-самцов Вистар, которым вводили подкожно Докс (2 мг/кг/нед.) в течение 5 недель (группа Докс). Животным группы Докс+ПМ наряду с доксорубицином 5 недель подкожно вводили ПМ в дозе 0,32 мг/кг ежедневно. Контрольной группе животных в течение 5 недель вводили такой же объем физиологического раствора. Перед началом введения препаратов и через 8 недель у всех крыс была выполнена эхокардиография (ЭхоКГ) левого желудочка (ЛЖ). Дополнительно у части животных была изучена сократительная функция ЛЖ при помощи PV-катетера. Содержание адениннуклеотидов (АТФ, АДФ и АМФ), фосфокреатина (ФКр), креатина (Кр) и лактата в безбелковых экстрактах сердец определяли энзиматическими методами. Дыхание митохондрий в скинированных сапонином волокнах ЛЖ определяли полярографическим методом. Результаты. В конце исследования у животных группы Докс фракция выброса и фракция укорочения были достоверно снижены, а диастолический объём ЛЖ уменьшен по сравнению с этими показателями в контрольной группе. В группе Докс+ПМ фракция выброса, фракция укорочения, индекс сократимости миокарда, максимальная скорость развития давления и работа сердца были выше, чем в группе Докс и недостоверно отличались от величин в контроле. Эти изменения сочетались с достоверным увеличением содержания общего фонда адениннуклеотидов и креатина в сердце животных группы Докс+ПМ по сравнению с этими показателями у животных, получавших только Докс. Показатели скорости дыхания митохондрий в волокнах ЛЖ, выделенных из сердец животных группы Докс+ПМ, были выше, чем в группе Докс. Заключение. Применение ПМ предотвращало развитие систолической дисфункции у животных, получавших Докс. Это было связано с улучшением окислительного фосфорилирования и сохранением фонда адениннуклеотидов в сердце Summary Aim. This study was designed to explore effects of the mitochondrial antioxidant plastomitin (PM) on the energy state and heart function of rats with cardiomyopathy induced by doxorubicin (Dox) administration. Material and methods. Male Wistar rats were injected subcutaneously with Dox (2 mg / kg / weekly) for 5 weeks (Dox group). Animals of the Dox + PM group were subcutaneously injected with PM for 5 weeks at a dose of 0.32 mg/kg daily along with Dox. The control group of animals was injected for 5 weeks with the same volume of saline. Before the administration of drugs and after 8 weeks of the study, all rats were underwented echocardiography of the left ventricle (LV). Additionally, the LV contractile function was studied using a PV catheter in some animals. The contents of adenine nucleotides (ATP, ADP and AMP), phosphocreatine (PCr), creatine (Cr) and lactate in protein-free extracts of hearts were determined by enzymatic methods. Mitochondrial respiration in saponin-skinned LV fibers was determined using the polarographic method. Results. At the end of the study, in animals of Dox group, the ejection fraction, fractional shortening and LV diastolic volume were significantly reduced in comparison with these indices in the control group. In Dox + PM group, the ejection fraction, fractional shortening, myocardial contractility index, maximum rate of pressure development and heart work were significantly higher than in Dox group and did not differ from the control values. These functional alterations were combined with a significant increase in the content of myocardial adenine nucleotide pool and creatine in animals of Dox + PM group compared with these parameters in animals treated with Dox alone.The rate of mitochondrial respiration in LV fibers isolated from the hearts of animals of Dox + PM group was higher than in Dox group. Conclusion. Treatment with PM prevented the development of LV systolic dysfunction in animals received Dox. This beneficial effect was due to an improvement in oxidative phosphorylation and preservation of myocardial adenine nucleotide pool.

scholarly journals Ex Vivo Cardiotoxicity of Antineoplastic Casiopeinas Is Mediated through Energetic Dysfunction and Triggered Mitochondrial-Dependent Apoptosis

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Christian Silva-Platas ◽  
César A. Villegas ◽  
Yuriana Oropeza-Almazán ◽  
Mariana Carrancá ◽  
Alejandro Torres-Quintanilla ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Cyclosporine A ◽  
Mechanical Performance ◽  
Mitochondrial Permeability Transition ◽  
Contractile Function ◽  
Ex Vivo ◽  
Significant Loss ◽  
Retention Capacity ◽  
Mitochondrial Permeability

Casiopeinas are a group of copper-based antineoplastic molecules designed as a less toxic and more therapeutic alternative to cisplatin or Doxorubicin; however, there is scarce evidence about their toxic effects on the whole heart and cardiomyocytes. Given this, rat hearts were perfused with Casiopeinas or Doxorubicin and the effects on mechanical performance, energetics, and mitochondrial function were measured. As well, the effects of Casiopeinas-triggered cell death were explored in isolated cardiomyocytes. Casiopeinas III-Ea, II-gly, and III-ia induced a progressive and sustained inhibition of heart contractile function that was dose- and time-dependent with an IC50 of 1.3 ± 0.2, 5.5 ± 0.5, and 10 ± 0.7 μM, correspondingly. Myocardial oxygen consumption was not modified at their respective IC50, although ATP levels were significantly reduced, indicating energy impairment. Isolated mitochondria from Casiopeinas-treated hearts showed a significant loss of membrane potential and reduction of mitochondrial Ca2+ retention capacity. Interestingly, Cyclosporine A inhibited Casiopeinas-induced mitochondrial Ca2+ release, which suggests the involvement of the mitochondrial permeability transition pore opening. In addition, Casiopeinas reduced the viability of cardiomyocytes and stimulated the activation of caspases 3, 7, and 9, demonstrating a cell death mitochondrial-dependent mechanism. Finally, the early perfusion of Cyclosporine A in isolated hearts decreased Casiopeinas-induced dysfunction with reduction of their toxic effect. Our results suggest that heart cardiotoxicity of Casiopeinas is similar to that of Doxorubicin, involving heart mitochondrial dysfunction, loss of membrane potential, changes in energetic metabolites, and apoptosis triggered by mitochondrial permeability.

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