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Oxidative stress represents a significant risk factor for the accelerated development of atherosclerosis in a population of patients on regular hemodialysis. Oxidative stress induced by hemodialysis can be triggered with both the bioincompatibility of dialysis membrane and increased endotoxin concentration in a hemodialysis solution. The aim of this study was to investigate the correlation between the parameters of oxidative stress, microinflammation, nutrition, secondary hyperparathyroidism and carotid artery intima-media thickness in patients on regular hemodialysis.One hundred and twenty five patients treated with standard hemodialysis and on-line hemodiafiltration with "high-flux" polysulfone dialysis membrane were examined. The following parameters of oxidative stress were measured : index of lipid peroxidation - measured as TBARS, nitric oxide in the form of nitrite - NO2-, super oxide anion radical - O2- and hydrogen peroxide - H2O2, catalase, superoxide dismutase (SOD) and reduced glutathione activity. For statistical analysis of results, the following tests were used: the Kolmogorov-Smirnov test, the Spirman test and the Pearson correlation test. Oxidative stress affects atherosclerosis of the carotid arteries in patients treated with regular hemodialysis and online hemodiafiltration. There is a statistically significant positive correlation between H2O2 concentration and the thickness of the carotid arteries` intima-media. High statistically significant positive correlation was found between TBARS concentration and carotid arteries intima-media thickness, while a high statistically significant negative correlation was found between SOD activity and a carotid artery intima-media thickness. There is a statistically significant negative correlation between the serum albumin and prealbumin concentration and a carotid artery intima-media thickness. Oxidative stress may be a significant risk factor for the carotid artery atherosclerosis development in patients treated with regular hemodialysis.

(1) Background: The aim of our study was to determine the role of oxidative stress (OS) during early evaluation of acute ST-elevated myocardial infarction (STEMI) and non-ST-elevated myocardial infarction (NSTEMI) patients in order to define the role of redox balance in profiling the development of myocardial infarction (MI). (2) Methods: This prospective observational case-control study included 40 consecutive STEMI and 39 NSTEMI patients hospitalized in the coronary care unit of the cardiology clinic at the Kragujevac Clinical Center, Serbia, between 1 January 2016 and 1 January 2017. Blood samples were collected from all patients for measuring cardio-specific enzymes at admission and 12 h after admission to evaluate systemic oxidative stress biomarkers and the activity of antioxidant enzymes. (3) Results: In this study, participants were predominately female (52%), with a mean age of 56.17 ± 1.22 years old in the STEMI group and 69.17 ± 3.65 in the non-STEMI group. According to the Killip classification, the majority of patients (>50%) were at the second and third level. We confirmed the elevation of superoxide anion radicals in the non-STEMI group 6 h after admission in comparison with the STEMI and CTRL groups, but levels had decreased 12 h after admission. Levels of hydrogen peroxide were statistically significantly increased in the NSTEMI group. A positive correlation of superoxide anion radicals and levels of troponin I at admission was observed (r = 0.955; p = 0.045), as well as an inverse correlation between reduced glutathione and levels of NT-pBNP measured 6 h after admission (r = −0.973; p = 0.027). (4) Conclusions: We confirmed that superoxide anion radicals and reduced glutathione observed together with hs-troponin I at admission and NT-pBNP during hospital treatment could be predictors of ST evolution.

The aim of this study was to examine and compare the influence of preconditioning, perconditioning, and postconditioning with creatine phosphate (PCr) on functional recovery and production of prooxidants in isolated rat hearts subjected to ex vivo ischemic–reperfusion (I–R) injury on a Langendorff apparatus. Wistar albino rats (male, n = 40) were divided into four groups: control and groups in which PCr (0.5 mmol/L, 5 min) was perfused before (Pre group), after (Post group), or during (Per group) ex vivo induced ischemia. PCr application was associated with the great benefits of preserving cardiac contractility (in Pre group 100.96% for +(d P/d t max) and 97.61% for −(d P/d t max), in Per group 96.72% for +(d P/d t max) and 95.60% for −(d P/d t max), and in Post group 143.84% for +(d P/d t max) and 104.36% for −(d P/d t max) in relation to the stabilization). In addition, PCr application prevented the increase in prooxidative markers during I–R injury in all therapeutic modalities. The most intensive benefits in the current investigation were observed when PCr was applied during the period of ischemia because the lowest fluctuations in the parameters of cardiac function and oxidative stress were observed. Overall, the results of this study highlight PCr-induced cardioprotection with promising prospects for future clinical use.

Energy drinks (EDs) contain caffeine and other active ingredients which affect cardiovascular system. The aims of this study were to examine direct effects of Red Bull (RB) on cardiodynamics and oxidative stress in isolated hearts of rats. The rats were divided into four groups: untrained rats who never consumed ED (dEDUT); untrained rats who consumed ED 5 days a week during 4 weeks (ch+dED-UT); rats trained 5 times a week for 4 weeks, but did not consume ED (dED-T); rats trained and consumed ED 5 times a week for 4 weeks (ch+dED-T). After sacrificing, hearts were isolated and perfused according to Langendorff technique. Through the isolated heart of all rats in each group, RB was administered. The parameters of cardiac function were recorded, and the levels of prooxidants were measured in the coronary effluent during coronary autoregulation. Rats in ch+dED-UT group had significantly lower rates of myocardial contraction and relaxation compared to rats in dED-UT group. The same effect was recorded in the dED-T group compared to dED-UT group. The levels of hydrogen peroxide were significantly higher in trained rats. Rats in ch+dED-T group also had significantly higher levels of superoxide anion radical and index of lipid peroxidation, as well as lower levels of nitrites when compared to ch+dED-UT group, while opposite effect was recorded in rats in dED-T group compared to dEDUT group. The RB could have a potentially negative inotropic effect in chronic consumers. Prooxidative effect of RB was most pronounced in trained chronic consumers.

Introduction. There are still no definite curative or preventive strategies for COVID-19 disease. It is crucial to fully comprehend the pathogenesis of COVID-19 infection so that we can develop expedient pharmacological protocols. While the impact of cytokine storm on COVID-19 severity has been one of the most tested hypotheses, the role of bradykinin and various other oxidative stress markers has been relatively under-researched. Their levels can be determined immediately after a hospital admission so they could be used as early predictors of the further development of the disease. Aim. The study aims at evaluating the possibility of using bradykinin and galectin-3 levels as early predictors that COVID-19 disease will progress into a severe case. Material and methods. The study was conducted as a prospective cross-sectional study. It included 47 consecutive adult patients with confirmed SARS-CoV-2 infection and COVID-19 pneumonia. All study subjects were admitted for a hospital treatment to the tertiary Clinical Hospital Center Bezanijska kosa, Belgrade, Serbia on June 2021. The blood samples were collected at the patients’ admission. The analyses of demographic, radiological, and clinical data were later conducted for both groups (the deceased patients and those who survived). In addition, we analyzed the potential relations between the outcome and the levels of bradykinin and galectin-3 measured immediately after the patients were admitted to the hospital. Results. The patients who passed away were predominantly older men with comorbidities. We recorded higher CT scores in the deceased patients and the significantly higher levels of urea, creatinine, CK, troponine, CRP, and other laboratory markers. They stayed at the ICU unit longer and required mechanical ventilation more frequently than the patients who survived. On the other hand, no differences were recorded in the time periods passing from the onset of the systems to the hospital admissions. Finally, we can highlight several independent predictors of mortality in patients with COVID-19 pneumonia, including the following: (1) patients who are 50 or more years old, (2) with in-hospital stays are longer that 4 days, (3) bradykinin levels surpass 220000 pg/ml, (4) D-dimer, creatinine, and CRP are elevated, and (5) comorbidities were present (such as hypertension and diabetes). Conclusion. The present study strongly supports the bradykinin storm hypothesis. Since elevated bradykinin levels have been found in most COVID-19 cases with fatal outcomes, the future therapeutical strategies for COVID-19 have to be focused on reducing bradykinin serum concentrations.

Abstract. Considering that sex related differences in cardiac response to flaxseed (FSO) and evening primrose oil (EPO) are insufficiently known present investigation assessed the effect of these two oils, on the cardiac function of isolated rat hearts and the possible role of sex in this. The present study was carried out on 60 adult male Wistar albino rats randomly divided into 6 groups: male rats treated with EPO, dose of 10 mg/kg/day; female rats treated with EPO, dose of 10 mg/kg/day; male rats treated with FSO, dose of 300 mg/kg/day; female rats treated with FSO, dose of 300 mg/kg/day; control group of female rats treated with regular laboratory diet for animals; control group of male rats treated with regular laboratory diet for animals. Using the Langendorff technique, markers of the heart function were evaluated: the maximum and minimum rates of pressure development in the left ventricle (LV; dP/dtmax, dP/dtmin), systolic and diastolic left ventricular pressure (SLVP, DLVP, respectively), heart rate (HR) and coronary flow (CF). Male rats treated with EPO had significantly higher (p = 0.016) mean values of dP/dtmax, dP/dtmin, SLVP and DLVP (average increase for all CPPs 20%, 25%, 30% and 110%, respectively), compared to the group of male rats treated with FSO (p = 0.914). Our study results indicate that both types of PUFA oils only slightly changed the function of the isolated rat heart in male but not in female rats. Nevertheless, the difference between oil treatments was found in male rats who had stronger cardiac response after supplementation with EPO.

Background/Aim. Energy drinks (EDs) are widely used by athletes as ergogenic agents and Red Bull? is one of the most consumed EDs among them. The aim of this study was to determine the acute and chronic effects of Red Bull? on cardiodynamics and parameters of oxidative stress in physically trained rats. Methods. Rats were subjected to a swimming practice (1h a day, 5 days a week, for 4 weeks). They were divided into 4 groups: rats that did not consume ED either before swimming or prior to sacrificing; rats that did not consume ED before swimming but did consume ED 30 min prior to sacrificing; rats that consumed ED 30 min before every swimming training but did not consume ED prior to sacrificing; rats that consumed ED 30 min before every swimming training and 30 min before sacrificing. After sacrificing, the hearts of the rats were isolated and perfused according to the Langendorff technique. The parameters of cardiac function were recorded, and also the levels of prooxidants were measured in the coronary effluent during coronary autoregulation. Results. Acute administration of the ED had a positive inotropic effect (manifested as a significantly higher level of the maximum and minimum rate of pressure development in the left ventricle), while chronic administration affected the isolated increase in systolic left ventricular pressure. The prooxidative effect of the ED was observed, which was more pronounced in chronic consumption. Conclusion. The main conclusion of our study is that chronic consumption of ED changes the cardiovascular response and redox status in acute consumption ED.

Background/Aim. Oxidative stress is an important risk factor for the development of cardiovascular atherosclerotic diseases in the population of patients treated with regular hemodialysis. Bioincompatibility of the dialysis membrane and increased concentration of endotoxin in the hemodialysis solution are two main factors that can trigger oxidative stress. This paper was intended to examine the effect of a vitamin E-coated membrane on oxidative stress during a single session of on-line hemodiafiltration. Methods. Twenty-four patients undergoing hemodiafiltration with vitamin E-coated polysulfone dialysis membrane (Leoceed 21H) were examined, followed by a polysulfone dialysis membrane treatment without vitamin E (FX800). The following parameters of oxidative stress were measured: superoxide anion radical (O2-), hydrogen peroxide (H2O2), thiobarbutyric acid reactive substances (TBARS), nitric oxide (NO2-), catalase (CAT), superoxide dizmutase (SOD), and reduced glutathione (GSH) activity. Statistical analysis included the Kolmogorov-Smirnov test, Student-t test and Wilcoxon test. Results. On-line hemodiafiltration using a high-flux polysulfone vitamin E-coated membrane led to significant reduction of TBARS concentration and SOD activity, while the on-line hemodiafiltration session using a high-flux polysulfone membrane that is not vitamin E-coated induced a significant increase in H2O2 concentration in the serum and a decrease in SOD activity. There was no statistical significance among the other parameters of oxidative stress. Conclusion. A single session of on-line hemodiafiltration using a vitamin E-coated polysulfone membrane significantly affects oxidative stress. After a single session of on-line hemodiafiltration using a vitamin E-coated membrane, the concentration of TBARS has significantly decreased. The decreased activity of superoxide dismutase could be a consequence of an increased loss of microelements during an on-line hemodiafiltration session using a high-flux polysulfone membrane. Patient selection, continuous on-line hemodiafiltration using a vitamin E-coated polysulfone membrane over a 3?6 month period and increased antioxidant protection capacity could possibly reduce the risk of cardiovascular morbidity and mortality in patients treated by hemodialysis.

The aim of our study was to investigate the influence of 12 weeks of consumption of chokeberry extract on redox status, body composition, lipid profile, and biochemical parameters in active handball players. The study included 16 handball players aged 16–24 years (20.26 ± 2.86 years). Every morning before training, players received 30 mL of liquid chokeberry extract for 12 weeks during the regular competition season. The research consisted of morphofunctional and biochemical testing, which was performed at three points (at the beginning of the study and at 6 and 12 weeks after extract consumption). After the chokeberry extract treatment, we observed significant changes in three main aspects. The 12 week supplementation with chokeberry extract decreased the levels of prooxidants (TBARS and nitrites) and increased catalase activity. Analyzing the dynamic of body composition showed a decrease in body fat (9.4 ± 0.5 vs. 7.3 ± 0.6 kg) as well as its percent in a body (11.4 ± 0.4% vs. 8.8 ± 0.4%). On the other hand, the analysis showed an increase of high-density lipoprotein (1.3 ± 0.3 vs. 1.6 ± 0.2 mmol/L) and hemoglobin (144.4 ± 11.7 vs. 151.7 ± 9.9 g/L) after 6 weeks of treatment. At the same time, a decrease in leukocytes (7.2 × 109 ± 2.8 vs. 6.5 ± 1.2 × 109/L) and an increase in red blood cells count (4.9 ± 0.4 × 109 vs. 5.5 ± 0.5 × 109/L) were observed. Overall, these results emphatically show that the use of chokeberry extract dietary supplement induced a wide range of beneficial effects in the examined group of athletes.

Background/Aim. Mechanisms responsible for the beneficial effects of aerobic exercise training on cardiovascular function are well known, but detraining effects on myocardial parameters have not been adequately elucidated. Therefore, the study aimed to determine the occurrence and speed of cardiac adaptation reversibility after the cessation of aerobic exercise and to reveal gender differences in achieved effects of training/detraining. Methods. Fe-male and male Wistar albino rats were divided into the following groups: control, trained, and two detrained groups. Hearts were perfused according to the Langendorff technique and the following cardiodynamic parameters were determined: the maximum and minimum rate of pressure development in the left ventricle (dp/dt max and dp/dt min, respectively), systolic and diastolic left ventricular pressure (SLVP and DLVP, respectively), heart rate (HR), and coronary flow. Results. Training significantly reduced values of dp/dt max, dp/dt min, and SLVP in males and females, and coronary flow in males. Detraining caused a reversion of those changes, which was gender-specific. In females, levels of SLVP were higher after 4 weeks of detraining compred to training, and after 2 weeks of detraining. Values of SLVP were lower in both detraining periods compared to training in males. Males had higher coronary flow after 2 weeks of detraining. Simultaneously, coronary flow was reduced in the 4th week of detraining in females. Conclusion. By using a model of the isolated rat heart, the present study confirmed the existence of training-induced changes in cardiac function. Cessation of training was followed by the loss of those adaptations, faster in males than females.

The aim of our study was to assess and compare the effects of dipeptidyl peptidase 4 (DPP4) inhibitors, saxagliptin and sitagliptin, on metabolic control of disease and cardiac function in rats with diabetes mellitus type 2 (T2DM). This research would provide novel understanding into the potentially protective effects of DPP4 inhibitors in helping salvage of the heart exposed to ischaemia-reperfusion (I-R) injury. Forty-eight Wistar albino rats were randomly divided into four groups: CTRL, Control healthy group; T2DM, rats with T2DM; T2DM + Sit, rats with T2DM treated with 0.6 mg/kg of sitagliptin; T2DM + Sax, rats with T2DM treated with 0.45 mg/kg of saxagliptin for 3 weeks. At the end of the protocol, in vivo cardiac function was assessed by echocardiography, while in the blood samples glucose and insulin were determined. Additionally, ex vivo heart function was estimated on a model of I-R injury using Langendorff apparatus. Immunohistochemical analysis was used to determine the degree of myocardial apoptosis and necrosis, while DPP4 staining was performed to assess the cardiac DPP4 expression. Data were analyzed using a one-way analysis of variance (ANOVA) and the post hoc Bonferroni test for multiple comparisons. Improved glycoregulation was noticed in rats that received DPP4 inhibitors compared to untreated diabetic rats (P < .05). Moreover, better in vivo systolic function was observed in rats treated with both DPP4 inhibitors as evidenced by an increase in fractional shortening when compared to T2DM (P < .05). Most parameters of cardiac function in treated rats remained unaltered during reperfusion, thus suggesting that both drugs protected myocardium during flow restoration. Better effects on coronary circulation were achieved after sitagliptin application. Additionally, both DPP4 inhibitors showed similar potential to attenuate cardiac necrosis and apoptosis. Saxagliptin and sitagliptin might be efficient in preserving myocardial function and morphology in ex vivo induced I-R cardiac injury in rats with T2DM.

Diabetes mellitus is a major risk factor for cardiovascular diseases, while cardiovascular diseases are a leading cause of morbidity and mortality worldwide. The renin–angiotensin– aldosterone system controls renal, cardiovascular, adrenal function and regulates fluid and electrolyte balance as well as blood pressure. Because of his role, inhibition of reninangiotensin-aldosteron system is another therapy approach that reduces the risk of diabetes and cardiovascular disease. In this study, our goal was to evaluate effect of valsartan,as inhibitor of angiotensin II receptor type 1, on cardiac tissue and function, with focus on cardiodynamic and oxidative stress. The present study was carried out on 20 adult male Wistar albino rats (8 week old and with body masses of 180-200 g). Rats were divided randomly into 2 groups (10 animals per group). Healthy animals treated with 1 μM of valsartan and streptozotocin-induced diabetic animals perfused with 1 μM of valsartan 4 weeks after the induction of diabetes. Our results demonstrated that acute application of valsartan has different effect on cardiodynamics in rat heart of diabetic and healthy animals but did not improve cardiac function in hyperglycemia-induced changes. A challenge for further investigations are studies with chronic or acute administration, alone or in combination with other angiotensin-converting-enzyme inhibitor in various models of diabetes.

Previous studies have demonstrated that individuals with type 2 diabetes mellitus (T2DM) have a two- to fourfold propensity to develop cardiovascular disease (CVD) than nondiabetic population, making CVD a major cause of death and disability among people with T2DM. The present treatment options for management of diabetes propose the earlier and more frequent use of new antidiabetic drugs that could control hyperglycaemia and reduce the risk of cardiovascular events. Findings from basic and clinical studies pointed out DPP-4 inhibitors as potentially novel pharmacological tools for cardioprotection. There is a growing body of evidence suggesting that these drugs have ability to protect the heart against acute ischaemia-reperfusion injury as well as reduce the size of infarction. Consequently, the prevention of degradation of the incretin hormones by the use of DPP-4 inhibitors represents a new strategy in the treatment of patients with T2DM and reduction of CV events in these patients. Here, we discuss the cardioprotective effects of DPP-4 inhibitors as well as proposed pathways that these hypoglycaemic agents target in the cardiovascular system.

The aim of this study was to estimate the effects of natural low mineral water from the source "Sneznik-1/79" in Serbia on glycemia as well as heart function in rats with diabetes mellitus type 2 (T2DM), with the special emphasis on the role of the oxidative stress. Twenty Wistar albino rats (males, 4 weeks old at the beginning of the study, body weight 180 ± 20 g) were included in the study. Rats were divided randomly into 2 groups (10 animals per group): T2DM: rats with diabetes mellitus type 2 with free access to tap water; T2DM + SW: rats with diabetes mellitus type with free access to natural mineral water from "Sneznik-1/79". Glucose level, ex vivo cardiac function as well as systemic and cardiac redox state were assessed. At the end of the study protocol, glucose level was lower in diabetic rats who consumed mineral water. Moreover cardiac function wasn't affected by mineral water intake, however, significant antioxidant effects were observed. Our study suggests that 4-week consumption of low mineral water from the spring "Sneznik-1/79" has important role in regulation of glycemia and altering redox state in favor of elevated antioxidant capacity without affecting heart function. Based on our findings we may assume that low mineral water from the spring "Sneznik-1/79" has the potential to be used either as preventive strategy or as additional therapeutic strategy in management of T2DM.

The aim of the study was to investigate the effects of chronic nandrolone decanoate treatment and/or swimming training on immunohistomorphometric parameters on rat pituitary gonadotropic cells. Male Wistar albino rats, 10 weeks old, were classified into four groups: control (T−N−), nandrolone (T−N+), swimming training (T+N−), and swimming training with nandrolone (T+N+). The T+ groups swam for 4 weeks, 1 h/day, 5 days/week. The N+ groups received nandrolone decanoate (20 mg/kg) once per week for 4 weeks. Pituitary tissue sections were processed and stained for immunohistochemical analysis and immunofluorescence. The volume density of luteinizing hormone (LH) cells was decreased by 48% in T−N+ and for 35% in the T+N+ group. The volume density of follicle-stimulating hormone (FSH) cells was decreased by 39% in T−N+ and for 30% in T+N+ compared to the control. Nandrolone alone, or combined with swimming training, decreased the number of LH/FSH cells compared to the control. The levels of the immunofluorescent signal of LH/FSH cells were increased in all experimental groups. Nandrolone alone decreased the serum level of LH by 17%, whereas swimming training alone increased FSH levels by 11% compared to the control. Serum levels of testosterone were increased in all experimental groups. Nandrolone alone, or combined with swimming training, decreased immunohistomorphometric parameters of gonadotropic cells, whereas the levels of immunofluorescent signal were increased.

At the end of 2019, a new coronavirus infection occurred in the People's Republic of China with an epicentre in the city of Wu-han On February 11th, 2020, the World Health Organization as-signed the official name of the infection caused by the new coro-navirus – COVID-19 COVID-19 has affected people from all over the world given that the infection was noted in 200 countries resulting in annunciation of the pandemic situation Human co-rona viruses cause mild to moderate respiratory infections At the end of 2002, a new coronavirus appeared (SARS-CoV), the causal agent of atypical pneumonia, which caused acute respiratory distress syndrome (ARDS) The initial stage of COVID-19 infection is the penetration of SARS-CoV-2 into target cells that have angi-otensin converting enzyme type II receptors The virus enters the body through the respiratory tract and interacts primarily with toll-like receptors (TLRs) The events in SARS-Cov-2 induced infection follow the next scenario: epithelial cells via TLRs recog-nize and identify SARS-Cov-2, and after that the information is transmitted to the transcriptional NF-κB, which causes expression of the corresponding genes Activated in this way, the epithelial cells begin to synthesize various biologically active molecules The results obtained on preclinical material indicate that ROS generation increases and the antioxidant protection decreases, which plays a major role in the pathogenesis of SARS-CoV, as well as in the progression and severity of this respiratory disease © 2020, University of Kragujevac, Faculty of Science All rights reserved

The present study aimed to estimate the effects of high-protein diet (PD)—isolated whey protein and omega-3 fatty acids—docosahexaenoic and eicosapentaenoic acid on oxidative parameters of rats treated with Olanzapine (OLZ). Experiments were carried out on 8-week-old Wistar albino male rats (n = 64) weighing 200 ± 20 g. By dietary and pharmacological treatment, all animals were divided into 8 groups: 1. CTRL group; 2. CTRL + OLZ group; 3. CTRL + FA group; 4. CTRL + OLZ + FA group; 5. PD group; 6. PD + OLZ group; 7. PD + FA group; 8. PD + OLZ + FA group. After 6 weeks of pharmacological/diet treatment, all animals were sacrificed to collect blood samples and determine the biomarkers of oxidative stress. The following oxidative stress markers were measured spectrophotometrically: superoxide anion radical (O2−), hydrogen peroxide (H2O2), nitric oxide (NO−), index of lipid peroxidation measured as TBARS, reduced glutathione, catalase and superoxide dismutase. The study has shown that Olanzapine treatment was associated with increased release of pro-oxidants and diminished activity of anti-oxidant markers. Additional supplementation with PD and FA succeeded in abolishing the negative influence in most of the measured parameters. However, these beneficial impacts were stronger in the case of their separate application, which could be the practical and clinical importance of these results.

Hypertension presents one of the main risk factors for cardiovascular diseases which are the leading cause of morbidity and mortality worldwide. Structural and mechanical changes of the heart and blood vessels as well as overproduction of reactive oxygen species may occur due to the increased blood pressure. Therewith, the goal of our study was to estimate the effects and duration of swimming as a possible therapy approach on blood pressure and oxidative stress parameters in normotensive and hypertensive rats. The study was conducted on 60 male Wistar albino rats divided into two groups, normotensive and hypertensive rats. Each of these groups was divided into three subgroups according to the swimming protocol. The swimming training was kept constant (60 min/day, for five days a week) with two days of rest. After six or nine weeks of the swimming protocol, blood pressure and oxidative stress markers were measured. The control group rats were put in water for one minute a day, in order to avoid water-induced stress. Training significantly reduced systolic blood pressure in hypertensive rats, while diastolic pressure did not change in the group that swam six or nine weeks. The results showed that swimming increases the activity of all measured antioxidative parameters, while values of prooxidants varied depending on the training protocol. Our results confirmed that swimming, as an aerobic exercise, decreases blood pressure and has time-dependent positive system adaptations, especially on the antioxidant parameters.

Up until now, the specific mechanisms involved in doxorubicin (DOX)-induced cardiotoxicity have not been fully elucidated. Since thiamine deficiency is associated with myocardial dysfunction and it may lead to cardiomyopathy, we aimed to investigate whether thiamine (Vitamin B1) treatment provides cardioprotection and modulates DOX mediated subchronic cardiotoxicity as well as to determine possible mechanisms of its effects. The study involved 48 Wistar albino rats divided into four groups: healthy non-treated rats and healthy rats treated with thiamine and DOX rats without treatment and DOX rats treated with thiamine. DOX was applied as a single i.p.injection (15mg/kg), while thiamine treatment lasted 7days (25mg/kg/dayi.p.). Before and after the treatment hemodynamic changes were monitored in vivo by echocardiography. When the protocol was completed, animals were sacrificed and rat hearts were isolated in order to evaluate parameters of cardiac oxidative stress [superoxide anion radical-O2−, hydrogen peroxide-H2O2, nitric oxide-NO−, index of lipid peroxidation-thiobarbituric acid (TBA) reactive substances (TBARS), superoxide dismutase – SOD, catalase (CAT), and reduced glutathione-GSH] and apoptosis (Bax, Bcl-2, caspases). DOX treatment significantly reduced the ejection fraction, while thiamine treatment led to its minor increase in the DOX-treated group. In that sense, heart oxidative stress markers were significantly increased in DOX-treated rats, while therapeutic dose of thiamine decreased the levels of free radicals. Our study demonstrated the promising ameliorative effects of thiamine against DOX-induced cardiotoxicity through modulation of oxidative stress, suppression of apoptosis, and possibility to improve myocardial performance and morphometric structure of rats` hearts.

N-methyl-D-aspartate receptor (NMDAR) belongs to iono-tropic glutamate receptor family. The most prominent roles of the NMDAR are related to the physiological and pathophysiological processes of the central nervous system (CNS). The link between NMDAR and cardiovascular pathology came into focus due to detrimental effects of homocysteine on the cardiovascular system. Regarding the fact that NMDAR affects Ca2+ homeostasis in cells, one of the main mechanisms which mediate adverse effects of glutamate dyshomeostasis and abnormal NMDAR activity is oxidative stress. Both in ischemia and during reperfusion, there are imbalance in Ca2+ and production of reactive species, which remains one of the basic mechanisms underlining the overall cardiomyocyte death due to myocardial infarction. The aim of this study was to assess the effects of blockade of NMDAR in heart using MK-801, in preconditioning and postconditioning fashion and to compare the values of oxidative stress biomarkers. We used Langendorff technique of isolated heart. In the control group, all isolated rat hearts were subjected to global ischemia after stabilization period (perfusion of the whole heart with Krebs-Henseleit solution was stopped) for 20 minutes, followed by 30 minutes of reperfusion. In the preconditioning group, after stabilization period, hearts were perfused with MK-801 for 5 minutes, before global ischemia of 20 minutes which was followed by 30 minutes reperfusion. In the postconditioning group, hearts were perfused with MK-801 during the first 3 minutes of reperfusion. Results of this study showed antioxidative effects of NMDAR inhibition in pre- and postconditioning of the isolated rat heart.

The investigation was aimed to evaluate the effects of 3-weeks swimming exercise on blood pressure and redox status in high-salt-induced hypertensive rats. Male Wistar albino rats (n=40, 6 weeks old) were divided into 4 groups: 1. hypertensive rats that swam for 3 weeks; 2. sedentary hypertensive control rats; 3. normotensive rats that swam for 3 weeks; 4. sedentary normotensive control rats. Hypertensive animals were on high concentrated sodium (8% NaCl) solution for 4 weeks (period of induction of hypertension). After sacrificing, hearts were isolated and perfused according to Langendorff technique at gradually increased coronary per-fusion pressure from 40–120 cmH2O. The oxidative stress markers were determined in coronary venous effluent: the index of lipid peroxidation (measured as TBARS), nitrites (NO2 −), superoxide anion radical (O2 −) and hydrogen peroxide (H2O2). Swimming did not lead to significant changes in levels of TBARS, NO2 −, O2 − in any of compared groups while levels of H2O2 were significantly higher in swimming hyper-tensive group comparing to swimming normotensive group at coronary perfusion pressure of 80–120 cmH2O. Our results indicate that the short-term swimming start to reduce blood pressure. In addition it seems that this type of swimming duration does not promote cardiac oxidative stress damages.

The aim of this study was to evaluate the influence of acute kidney injury caused by high doses of folic acid on cardiac function and markers of oxidative stress in serum and isolated rat heart. Isolated hearts of Wistar albino rats (divided into two groups: control and folic acid group) were perfused according to Langendorff technique at basal coronary perfusion pressure CPP of 70 cm H2O. After a stabilization period, CPP was lowered to 60 cm H2O and then gradually increased to 80, 100, 120 and finally decreased to 40 cm H2O in order to establish coronary autoregulation. For each perfusion pressure value, the left ventricular function parameters were determined. Samples of coronary venous effluent were collected for determination of coronary flow and biomarkers of oxidative stress. The blood samples were collected in order to examine the values of serum urea, creatinine, Na, K, and parameters of oxidative stress and antioxidant defense system. Heart and kidney tissue samples were collected for histopathological examination. Folic acid group showed reduction of systolic and diastolic left ventricular pressure and increase of coronary flow and minimum left ventricular pressure development rate. In coronary flow, folic acid group showed increased levels of TBARS and reduction of H2O2 and NO2−. Serum ROS concentrations were lower in rats treated with folic acid, particularly levels of TBARS and NO2− in which values were significantly lower. The parameters of systemic antioxidative stress were at significantly high levels especially SOD and GSH. This study is the experimental confirmation of cardio-renal syndrome type 3, which represents the acute kidney injury that causes a damage of a heart function. The data suggest that negative effects of acute kidney injury on myocardium do not necessarily involve oxidative stress, which may lead to future investigations which will be based on inflammation as a one of the important factors in the organ crosstalk.

This study investigated different dietary strategies, high-fat (HFd), or standard diet (Sd) alone or in combination with standardized Aronia melanocarpa extract (SAE), as a polyphenol-rich diet, and their effects on lipids and fatty acids (FA) in rats with metabolic syndrome (MetS). Wistar albino rats were randomly divided into two groups: healthy and rats with MetS, and then depending on dietary patterns on six groups: healthy rats fed with Sd, healthy rats fed with Sd and SAE, rats with MetS fed with HFd, rats with MetS fed with HFd and SAE, rats with MetS fed with Sd, and rats with MetS fed with Sd and SAE. 4 weeks later, after an overnight fast (12-14 h), blood for determination of total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), index of lipid peroxidation (measured as TBARS), and FA was collected. Increased FA and lipid concentration found in MetS rats were reduced when changing dietary habits from HFd to Sd with or without SAE consumption. Consumption of SAE slightly affects the FA profiles, mostly palmitoleic acid in healthy rats and PUFA in MetS + HFd rats. Nevertheless, in a high-fat diet, SAE supplementation significantly decreases n-6/n-3 ratio, thereby decreasing systemic inflammation. Further researches are warranted to confirm these effects in humans.

The strong association among the risk of coronary artery diseases (CAD), high levels of LDL-C and low levels of HDLC is well established. Hyperhomocysteinaemia (HHcy) is an independent risk factor for cardiovascular disease (CVD) and causes endothelial dysfunction, a hallmark of atherosclerosis. In this study, we ascertained the influence of statins on the atherogenic index, as an indicator and a significant adjunct for predicting atherosclerosis in hyperhomocysteinaemic male Wistar albino rats. For 4 weeks, the animals were fed with one of the following diets (Mucedola SRL., Milan, Italy): standard rodent chow; a diet enriched in methionine with no deficiency in B vitamins or a diet enriched in methio-nine and deficient in B vitamins. The animals were simultaneously exposed to a pharmacology treatment with atorvastatin at dose of 3 mg/kg/day i.p. or simvastatin, at dose of 5 mg/kg/day i.p. We measured weight gain, food intake, and FER and determined the concentrations of biochemical parameters of dyslipidaemia (TC, TGs, LDL-C, VLDL-C, and HDL-C), AI, and CRR. A histopathological examination was conducted on portions of the right and left liver lobes from each animal. A connection between Hhcy and dyslipidaemia was indicated by the findings of biochemical and histological analyses, suggesting that Hhcy was a pro-atherogenic state. An improvement in the lipid profile along with a decrease in the atherogenic index by statins suggests that atorvastatin and simvastatin could be useful antiatherogenic agents, with protective activities during hyperhomocysteinaemia.

Polycystic ovary syndrome (PCOS) is a multifaced reproductive endocrinopathy affecting 6-20% of women of childbearing age. It was previously shown that women with PCOS have an increased risk of cardiovascular (CV) diseases. The aim of this study was to evaluate the cardiodynamic parameters of isolated rats’ hearts, blood pressure levels, and histomorphological changes in the heart tissue following the androgen-induced PCOS model in rats and the role of oxidative stress in the development of these CV properties of PCOS. 21-day-old female rats ( n = 12 ) were divided into control and PCOS groups. PCOS was induced by administration of testosterone enanthate (1 mg/kg BW, daily) during 35 days. During the autoregulation protocol (40-120 mmHg) on the Langendorff apparatus, ex vivo cardiodynamic parameters of retrogradely perfused hearts showed enhanced contractile function and increased lusitropic effects in the left ventricle (LV) in PCOS rats. Systolic and diastolic pressures in LV were elevated at all perfusion pressure values. Systemic arterial systolic blood pressure showed borderline elevation, while mean arterial blood pressure was significantly higher in PCOS rats. Histological evaluation of heart tissue depicted hypertrophic (8.3%) alterations in LV cardiomyocytes and increase (7.3%) in LV wall thickness. Oxidative stress parameters were altered in systemic circulation, coronary venous effluent (CVE), and heart tissue. Levels of superoxide dismutase and reduced glutathione were decreased in blood and heart tissue, while catalase activity was not altered. Degree of lipid peroxidation was increased in circulation as well as heart tissue. Increased levels of O2- in CVE indicated the cardiotoxic effects in the rat PCOS model. The mentioned alterations of oxidative stress parameters in the blood, CVE, and heart could be recommended as potential contributors underlying the development of CV risk in PCOS women.

Cardiovascular diseases are the leading cause of morbidity and mortality in patients with diabetes mellitus. Increased bioavailability of reactive oxygen species is defined as oxidative stress and is noticed in type 2 DM and reduced antioxidant enzymes expression/ activity. Aldosterone, an adrenal hormone, is secreted due to renin-angiotensin–aldosterone system activation, representing one of the fundamental physiological reactions in CVD. Spironolactone, a mineralocorticoid receptor antagonist, uses enhanced coronary microvascular function, suggesting a beneficial role of aldosterone in preventing diabetic cardiovascular complications in patients with type 2 DM. In this study, we evaluated the influence of spironolactone's acute administration on oxidative stress in rats with diabetes mellitus induced by streptozotocin. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μM of spironolactone, diabetic rats treated with 0.1 μM of spironolactone, healthy rats treated with 3 μM of spironolactone, and diabetic rats treated with 3 μM of spironolactone. Spironolactone achieved different effects on oxidative stress parameters when given acutely in different doses in diabetic and healthy rats. In lower doses, spironolactone's acute administration reached lowered parameters of oxidative stress in healthy rats better than higher doses of spironolactone. In contrast, in the diabetic group, acute effects of higher doses of spironolactone lowered oxidative stress parameters better than lower spironolactone doses.

Funding Acknowledgements Type of funding sources: None. Introduction Verapamil, a calcium channel blocker, is used for treatment of hypertension, paroxysmal supraventricular tachycardia and angina pectoris. It primarily blocks L-type calcium channels preventing excessive influx of calcium into cardiomyocytes, leading to negative inotropic effect, and smooth muscle cells resulting in reduced relaxation of vasculature. With calcium antagonism it also causes negative chronotropic effect. However, there is no data on it’s dose-dependent effects on cardiac dynamic parameters and heart rate on isolated rat heart with hypertension. Purpose To investigate chronic, dose-dependent effects of Verapamil on cardiodynamic parameters in isolated rat heart with hypertension. Methods The present 4-week study was carried out on 24 spontaneously hypertensive Wistar Kyoto male rats (6 weeks old): Control (n = 6), rats treated with 0.5 mg/kg/day of Verapamil (n = 6), rats treated with 5 mg/kg/day of Verapamil (n = 6) and rats treated with 50 mg/kg/day of Verapamil (n = 6). Isolated rat hearts were perfused on Langendorff perfusion apparatus. Results Chronic, low-dose Verapamil treatment significantly depressed function of all cardiodynamic parameters of the hypertensive heart when compared to the rats treated with higher doses of Verapamil (p Conclusions Chronic treatment with Verapamil in high dose achieved better inotropic, chronotropic and lusitropic effects than treatment in low and middle doses of Verapamil, without significant effects on coronary flow. There is dose-depended effect of chronic Verapamil treatment on cardiac function of isolated rat heart with hypertension.

The aim of our study was to investigate the effects of one-month consumption of polyphenol-rich standardized Aronia melanocarpa extract (SAE) on redox status in anemic hemodialysis patients. The study included 30 patients (Hb 3 months; > 3 times week). Patients were treated with commercially available SAE in a dose of 30 ml/day, for 30 days. After finishing the treatment blood samples were taken in order to evaluate the effects of SAE on redox status. Several parameters of anemia and inflammation were also followed. After the completion of the treatment, the levels of superoxide anion radical and nitrites significantly dropped, while the antioxidant capacity improved via elevation of catalase and reduced glutathione. Proven antioxidant effect was followed by beneficial effects on anemia parameters (increased hemoglobin and haptoglobin concentration, decreased ferritin and lactate dehydrogenase concentration), but SAE consumption didn`t improve inflammatory status, except for minor decrease in C-reactive protein. The consumption of SAE regulates redox status (reduce the productions of pro-oxidative molecules and increase antioxidant defense) and has beneficial effects on anemia parameters. SAE could be considered as supportive therapy in patients receiving hemodialysis which are prone to oxidative stress caused by both chronic kidney disease and hemodialysis procedure. Additionally, it could potentially be a good choice for supplementation of anemic hemodialysis patients. TRN: NCT04208451 December 23, 2019 “retrospectively registered”

Galectin-3 (Gal-3) is the only member of galectin family able to form pentamers and heterodimers with chemokines. Its presence in various cells and tissues suggests variety of regulatory functions in physiological conditions, but increasing body of evidence indicates involvement of Gal-3 in pathological cascades of many diseases. Gal-3 exerts different, sometimes opposite, effects in various disorders or in different phases of the same disease. These differences in action of Gal-3 are related to the localization of Gal-3 in the cell, types of receptors through which it acts, or the types of cells that secrete it. As a regulator of immune response and T-cell activity, Gal-3 appears to have important role in development of autoimmunity mediated by T cells. Absence of Gal-3 in C57Bl6 mice favors Th2 mediated inflammatory myocarditis but attenuate fibrosis. Recent data also indicate Gal-3 involvement in development atherosclerosis. In pathogenesis of diabetes type 1 and autoimmune components of diabetes type 2 Gal-3 may have detrimental or protective role depending on its intracellular or extracellular localization. Gal-3 mediates autoimmune hepatic damage through activation of T-cells or natural killer T cells. Gal-3 is an important mediator in neurodevelopment, neuropathology and behavior due to its expression both in neurons and glial cells. All together, assessing the role of Gal-3 in immunopathology and autoimmunity it could be concluded that it is an important participant in pathogenesis, as well as promising monitoring marker and therapeutic target.

This study aimed to examine the effects of diallyl trisulfide (DATS), the most potent polysulfide derived from garlic, on metabolic syndrome and myocardial function in rats with metabolic syndrome (MetS). For that purpose, we used 36 male Wistar albino rats divided into control rats, rats with MetS and MetS rats treated with 40 mg/kg of DATS every second day for 3 weeks. In the first part, we studied the impact of DATS on MetS control and found that DATS significantly raised H2S, decreased homocysteine and glucose levels and enhanced lipid and antioxidative, while reducing prooxidative parameters. Additionally, this polysulfide improved cardiac function. In the second part, we investigated the impact of DATS on ex vivo induced ischemia/reperfusion (I/R) heart injury and found that DATS consumption significantly improved cardiodynamic parameters and prevented oxidative and histo-architectural variation in the heart. In addition, DATS significantly increased relative gene expression of eNOS, SOD-1 and -2, Bcl-2 and decreased relative gene expression of NF-κB, IL-17A, Bax, and caspases-3 and -9. Taken together, the data show that DATS can effectively mitigate MetS and have protective effects against ex vivo induced myocardial I/R injury in MetS rat.

Ruthenium(II) complexes offer the potential for lower toxicity compared with platinum(II) complexes. Our study aimed to compare cardiotoxicity of [Ru(Cl-tpy)(en)Cl][Cl], [Ru(Cl-tpy)(dach)Cl][Cl], [Ru(Cl-tpy)(bpy)Cl][Cl], cisplatin, and saline through assessment of redox status and relative expression of apoptosis-related genes. A total of 40 Wistar albino rats were divided into five groups. Ruthenium groups received a single dose of complexes intraperitoneally (4 mg/kg/week) for a 4-week period; cisplatin group received cisplatin (4 mg/kg/week) and control group received saline (4 mL/kg/week) in the same manner as ruthenium groups. In collected blood and heart tissue samples, spectrophotometric determination of oxidative stress biomarkers was performed. The relative expression of apoptosis-related genes (Bcl-2, Bax, and caspase-3) in hearts was examined by real-time polymerase chain reaction. Our results showed that systemic and cardiac pro-oxidative markers (thiobarbituric acid reactive substances and nitrite) were significantly lower in ruthenium groups compared with cisplatin group, while concentrations of antioxidative parameters (catalase, superoxide dismutase, and oxidized glutathione) were significantly higher. Ruthenium administration led to significantly lower gene expression of Bax and caspase-3 compared with cisplatin-treated rats, while Bcl-2 remained unchanged. Applied ruthenium complexes have less pronounced potential for induction of oxidative stress-mediated cardiotoxicity compared with cisplatin. These findings may help for future studies that should clarify the mechanisms of cardiotoxicity of ruthenium-based metallodrugs.