Browsing by Author "Zivkovic, Vladimir (55352337400)"

Extensive experimental evidence confirms the role of oxidative stress as a major contributor to the pathogenesis of acute kidney injury (AKI). However, less information is available on the evolution of prooxidant-antioxidant parameters from early to end-phase renal function decline in humans. This study aimed to determine the oxidative status in dynamic throughout the evolutionary phases of the disease. The study included patients with cardiovascular pathology and AKI hospitalized in the intensive care unit (n = 69) and age-matched healthy controls (n = 30). They were followed through three phases of AKI; first phase was the phase of diagnosis, which is characterized by oliguria/anuria, second phase was established diuresis, and third phase was the polyuric phase. In these phases of the disease, blood samples were taken from the patients for biochemical analysis. From the collected whole blood, we measured spectrophotometrically prooxidants: index of lipid peroxidation, measured as Thiobarbituric acid reactive substances (TBARS), nitrite (NO 2 – ), superoxide anion radical (O 2 – ) and hydrogen peroxide (H 2 O 2 ), and antioxidants: activity of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) from erythrocyte lysate. Comparing the results of the three measurements, a significant difference was found in the levels of NO 2 – and GSH, both of which increased in the second phase (P < 0.05) and then decreased in the third phase, and a significant increase in TBARS, which was elevated in the second phase (P < 0.05) and did not change significantly until the third phase. Our results showed phase-dependent modification in 3 parameters of the oxidative status (TBARS, NO 2 – and GSH). Whether these changes contribute to the deterioration of renal function in AKI remains to be established. © 2015 by The Chinese Physiological Society and Airiti Press Inc.

Extensive experimental evidence confirms the role of oxidative stress as a major contributor to the pathogenesis of acute kidney injury (AKI). However, less information is available on the evolution of prooxidant-antioxidant parameters from early to end-phase renal function decline in humans. This study aimed to determine the oxidative status in dynamic throughout the evolutionary phases of the disease. The study included patients with cardiovascular pathology and AKI hospitalized in the intensive care unit (n = 69) and age-matched healthy controls (n = 30). They were followed through three phases of AKI; first phase was the phase of diagnosis, which is characterized by oliguria/anuria, second phase was established diuresis, and third phase was the polyuric phase. In these phases of the disease, blood samples were taken from the patients for biochemical analysis. From the collected whole blood, we measured spectrophotometrically prooxidants: index of lipid peroxidation, measured as Thiobarbituric acid reactive substances (TBARS), nitrite (NO 2 – ), superoxide anion radical (O 2 – ) and hydrogen peroxide (H 2 O 2 ), and antioxidants: activity of superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) from erythrocyte lysate. Comparing the results of the three measurements, a significant difference was found in the levels of NO 2 – and GSH, both of which increased in the second phase (P < 0.05) and then decreased in the third phase, and a significant increase in TBARS, which was elevated in the second phase (P < 0.05) and did not change significantly until the third phase. Our results showed phase-dependent modification in 3 parameters of the oxidative status (TBARS, NO 2 – and GSH). Whether these changes contribute to the deterioration of renal function in AKI remains to be established. © 2015 by The Chinese Physiological Society and Airiti Press Inc.

The strong association among the risk of coronary artery diseases (CAD), high levels of LDL-C and low levels of HDL-C 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 methionine 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. © 2019, University of Kragujevac, Faculty of Science. All rights reserved.

Objective. Hyperbaric oxygen (HBO) has been widely used in people with diseases that cause limb amputation but studies that target patients who underwent amputation itself are rare. The aim of our study was to investigate the effects of HBO on prosthetic rehabilitation in patients with unilateral lower limb amputation. Methods. The study included 60 patients with unilateral (left or right side) lower limb amputation, mean age 61.6 ± 11.5 years, of both genders. They were divided into two groups, the experimental group (with HBO) and the control group (usual care). Patients' functional skills after amputation were evaluated using the LCI test (Locomotor Capabilities Index) and with the classification of Narang and Pohjolainen. Results. Clinical characteristics of patients had relatively homogeneous distribution. After the therapy, a control measurement of both groups showed significantly higher values for LCI test (p <0.01) and lower values for Narang score (p <0.01). However, improvements were more prominent in the group of patients who underwent HBO therapy, therefore, these subjects in the control measurements were evaluated with a statistically significant lower Narang score (p <0.05) and had higher LCI score than the control group patients. Conclusion. HBO is a useful therapeutic measure in the rehabilitation of people with limb amputation who use prosthetic limbs.

Regular training has been claimed to increase the activity of antioxidant enzymes and, consequently, augments the resistance to oxidative stress; however, large volumes of training performed by elite sportsmen could lead to a chronic oxidative stress state. The aim of our study was to assess the oxidative status of elite athletes at the beginning of the preparatory and the beginning of the competition training phases, so that the influence of three months of programmed physical activity on redox status could be determined. The chronic effects of exercise on the redox state of the athletes were compared to the effects of a single bout of karate training. Thirty elite karate athletes, 16-30 years old, were subjected to maximal graded exercise test to estimate their aerobic capacity; blood sampling was also performed to measure levels of superoxide anion radical (O2-), hydrogen peroxide (H2O2), superoxide dismutase activity (SOD) and catalase activity (CAT). The only significant change after the three-month training process was found in the significantly decreased CAT activity (X ± SE: 7.95 ± 0.13 U/g Hb × 103 in the preparatory period, 6.65 ± 0.28 U/g Hb × 103 in the competition stage; P < 0.01). After a single karate training session, there was statistically significant decrease of O2- (X ± SE: 32.7 ± 4.9 nmol/ml in the preparatory period, 24.5 ± 2.5 nmol/ml in the competition stage; P < 0.05) and increase of H2O2 (X ± SE: 11.8 ± 1.0 nmol/ml in the preparatory period, 14.2 ± 0.9 nmol/ml in the competition stage; P < 0.01), as well as significant CAT increase (X ± SE: 6.6 ± 0.6 U/g Hb × 103 in the preparatory period, 8.5 ± 0.5 U/g Hb × 103 in the competition stage; P < 0.05). Although the three-month training process induced, at the first sight, negative changes in the redox state, expressed through the decrease in CAT activity, adequate response of the antioxidant system of our athletes to acute exercise was preserved. © 2012 by The Chinese Physiological Society and Airiti Press Inc.

Regular training has been claimed to increase the activity of antioxidant enzymes and, consequently, augments the resistance to oxidative stress; however, large volumes of training performed by elite sportsmen could lead to a chronic oxidative stress state. The aim of our study was to assess the oxidative status of elite athletes at the beginning of the preparatory and the beginning of the competition training phases, so that the influence of three months of programmed physical activity on redox status could be determined. The chronic effects of exercise on the redox state of the athletes were compared to the effects of a single bout of karate training. Thirty elite karate athletes, 16-30 years old, were subjected to maximal graded exercise test to estimate their aerobic capacity; blood sampling was also performed to measure levels of superoxide anion radical (O2-), hydrogen peroxide (H2O2), superoxide dismutase activity (SOD) and catalase activity (CAT). The only significant change after the three-month training process was found in the significantly decreased CAT activity (X ± SE: 7.95 ± 0.13 U/g Hb × 103 in the preparatory period, 6.65 ± 0.28 U/g Hb × 103 in the competition stage; P < 0.01). After a single karate training session, there was statistically significant decrease of O2- (X ± SE: 32.7 ± 4.9 nmol/ml in the preparatory period, 24.5 ± 2.5 nmol/ml in the competition stage; P < 0.05) and increase of H2O2 (X ± SE: 11.8 ± 1.0 nmol/ml in the preparatory period, 14.2 ± 0.9 nmol/ml in the competition stage; P < 0.01), as well as significant CAT increase (X ± SE: 6.6 ± 0.6 U/g Hb × 103 in the preparatory period, 8.5 ± 0.5 U/g Hb × 103 in the competition stage; P < 0.05). Although the three-month training process induced, at the first sight, negative changes in the redox state, expressed through the decrease in CAT activity, adequate response of the antioxidant system of our athletes to acute exercise was preserved. © 2012 by The Chinese Physiological Society and Airiti Press Inc.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats. © 2023 by the authors.

Homocysteine, an amino acid containing a sulfhydryl group, is an intermediate product during metabolism of the amino acids methionine and cysteine. Hyperhomocysteinemia is used as a predictive risk factor for cardiovascular disorders, the stroke progression, screening for inborn errors of methionine metabolism, and as a supplementary test for vitamin B12 deficiency. Two organic systems in which homocysteine has the most harmful effects are the cardiovascular and nervous system. The adverse effects of homocysteine are achieved by the action of several different mechanisms, such as overactivation of N-methyl-D-aspartate receptors, activation of Toll-like receptor 4, disturbance in Ca2+ handling, increased activity of nicotinamide adenine dinucleotide phosphate-oxidase and subsequent increase of production of reactive oxygen species, increased activity of nitric oxide synthase and nitric oxide synthase uncoupling and consequent impairment in nitric oxide and reactive oxygen species synthesis. Increased production of reactive species during hyperhomocysteinemia is related with increased expression of several proinflammatory cytokines, including IL-1α, IL-6, TNF-α, MCP-1, and intracellular adhesion molecule-1. All these mechanisms contribute to the emergence of diseases like atherosclerosis and related complications such as myocardial infarction, stroke, aortic aneurysm, as well as Alzheimer disease and epilepsy. This review provides evidence that supports the causal role for hyperhomocysteinemia in the development of cardiovascular disease and nervous system disorders. © 2018, Canadian Science Publishing. All rights reserved.

Homocysteine, an amino acid containing a sulfhydryl group, is an intermediate product during metabolism of the amino acids methionine and cysteine. Hyperhomocysteinemia is used as a predictive risk factor for cardiovascular disorders, the stroke progression, screening for inborn errors of methionine metabolism, and as a supplementary test for vitamin B12 deficiency. Two organic systems in which homocysteine has the most harmful effects are the cardiovascular and nervous system. The adverse effects of homocysteine are achieved by the action of several different mechanisms, such as overactivation of N-methyl-D-aspartate receptors, activation of Toll-like receptor 4, disturbance in Ca2+ handling, increased activity of nicotinamide adenine dinucleotide phosphate-oxidase and subsequent increase of production of reactive oxygen species, increased activity of nitric oxide synthase and nitric oxide synthase uncoupling and consequent impairment in nitric oxide and reactive oxygen species synthesis. Increased production of reactive species during hyperhomocysteinemia is related with increased expression of several proinflammatory cytokines, including IL-1α, IL-6, TNF-α, MCP-1, and intracellular adhesion molecule-1. All these mechanisms contribute to the emergence of diseases like atherosclerosis and related complications such as myocardial infarction, stroke, aortic aneurysm, as well as Alzheimer disease and epilepsy. This review provides evidence that supports the causal role for hyperhomocysteinemia in the development of cardiovascular disease and nervous system disorders. © 2018, Canadian Science Publishing. All rights reserved.

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Considering the limited data on the role of NMDA-Rs in the cardiovascular system, the aim of the present study was to examine the effects of NMDA and DL-Hcy TLHC, alone and in combination with glycine, memantine, and ifenprodil, in the isolated rat heart. The hearts of Wistar albino rats were retrogradely perfused according to the Langendorff technique at a constant perfusion pressure. The experimental protocol for all experimental groups included the stabilization period, application of estimated substance for 5 min, followed by a washout period of 10 min. Using a sensor placed in the left ventricle, we registered the following parameters of myocardial function: dp/dtmax, dp/dtmin, SLVP, DVLP, HR; CF was measured using flowmetry). We estimated the following oxidative stress biomarkers in the coronary venous effluent using spectrophotometry: TBARS, NO2−, O2−, and H2O2. NMDAalone did not induce any change in any of the observed parameters, while DL-Hcy TLHC alone, as well as a combined application of NMDA and DL-Hcy TLHC with glycine, induced a reduction of most cardiodynamic parameters. Memantine and ifenprodil induced a reduction of cardiodynamic parameters and CF, as well as some oxidative stress biomarkers. © 2017, Canadian Science Publishing. All rights reserved.

Considering the limited data on the role of NMDA-Rs in the cardiovascular system, the aim of the present study was to examine the effects of NMDA and DL-Hcy TLHC, alone and in combination with glycine, memantine, and ifenprodil, in the isolated rat heart. The hearts of Wistar albino rats were retrogradely perfused according to the Langendorff technique at a constant perfusion pressure. The experimental protocol for all experimental groups included the stabilization period, application of estimated substance for 5 min, followed by a washout period of 10 min. Using a sensor placed in the left ventricle, we registered the following parameters of myocardial function: dp/dtmax, dp/dtmin, SLVP, DVLP, HR; CF was measured using flowmetry). We estimated the following oxidative stress biomarkers in the coronary venous effluent using spectrophotometry: TBARS, NO2−, O2−, and H2O2. NMDAalone did not induce any change in any of the observed parameters, while DL-Hcy TLHC alone, as well as a combined application of NMDA and DL-Hcy TLHC with glycine, induced a reduction of most cardiodynamic parameters. Memantine and ifenprodil induced a reduction of cardiodynamic parameters and CF, as well as some oxidative stress biomarkers. © 2017, Canadian Science Publishing. All rights reserved.

Polycystic ovary syndrome (PCOS) is the most common complex endocrinological condition of women that is associated with infertility and metabolic disorders during the reproductive period. Recently, a great deal of research has focused on the etiopathogenesis of this disorder and the modulation of therapeutic approaches. There are still many controversies in the choice of therapy, and metformin is one of the most commonly used agents in the treatment of PCOS. Considering the link between metabolic disorders and PCOS, glycemic status is crucial in these patients, and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) represent a potentially promising new therapeutic approach. These drugs have been shown to improve glucose metabolism, reduce adipose tissue, decrease oxidative stress, and protect the cardiovascular system. These data prompted us to investigate the effects of empagliflozin (EMPA) in a PCOS rat model and compare them with the effects of metformin. We confirmed that EMPA positively affects somatometric parameters, glucose and lipid metabolism, and the levels of sex hormones, as well as reduces oxidative stress and improves ovarian function and morphology. Administration of EMPA at doses of 5 mg/kg, 15 mg/kg, and 45 mg/kg during a 4-week treatment period improved, as induced by estradiol valerate and a high-fat diet, the metabolic and reproductive statuses in a PCOS rat model. The best effects, which were comparable to the effects of metformin, were achieved in groups receiving the middle and highest applied doses of EMPA. These results may prompt further clinical research on the use of EMPA in patients with PCOS. © 2024 by the authors.

AIM: To examine the effects of nitroglycerine on portal vein haemodynamics and oxidative stress in patients with portal hypertension. METHODS: Thirty healthy controls and 39 patients with clinically verified portal hypertension and increased vascular resistance participated in the study. Liver diameters, portal diameters and portal flow velocities were recorded using color flow imaging/pulsed Doppler detection. Cross-section area, portal flow and index of vascular resistance were calculated. In collected blood samples, superoxide anion radical (O2-), hydrogen peroxide (H2O2), index of lipid peroxidation (measured as TBARS) and nitric oxide (NO) as a marker of endothelial response (measured as nitrite-NO2-) were determined. Time-dependent analysis was performed at basal state and in 10th and 15th min after nitroglycerine (sublingual 0.5 mg) administration. RESULTS: Oxidative stress parameters changed significantly during the study. H2O2 decreased at the end of study, probably via O2- mediated disassembling in Haber Weiss and Fenton reaction; O2-increased significantly probably due to increased diameter and tension and decreased shear rate level. Consequently O2- and H2O2 degradation products, like hydroxyl radical, initiated lipid peroxidation. Increased blood flow was to some extent lower in patients than in controls due to double paradoxes, flow velocity decreased, shear rate decreased significantly indicating non Newtonian characteristics of portal blood flow. CONCLUSION: This pilot study could be a starting point for further investigation and possible implementation of some antioxidants in the treatment of portal hypertension. © 2012 Baishideng. All rights reserved.

N-methyl-D-aspartate (NMDA) receptors belong to ionotropic glutamate receptor family, together with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, kainite receptors and δ-receptors. All of these receptors are tetramers composed of four subunits. NMDA receptors have several unique features in relation to other ionotropic glutamate receptors: requirement for simultaneous action of two coagonists, glutamate and glycine; dual control of receptor activation, ligand-dependent (by glutamate and glycine) and voltage-dependent (Mg2+ block) control; and influx of considerable amounts of Ca2+ following receptor activation. Increasing number of researches deals with physiological and pathophysiological roles of NMDA receptors outside of nerve tissues, especially in the cardiovascular system. NMDA receptors are found in all cell types represented in cardiovascular system, and their overstimulation in pathological conditions, such as hyperhomocysteinemia, is related to a range of cardiovascular disorders. On the other hand we demonstrated that blockade of NMDA receptors depresses heart function. There is a need for the intensive study of NMDA receptor in cardiovascular system as potential theraputical target both in prevention and treatment of cardiovascular disorders. © 2019, University of Kragujevac, Faculty of Science. All rights reserved.

Purpose: The idea behind this study was to assess the effects of empagliflozin and sacubitril/valsartan and their combination on isoproterenol-induced heart failure (HF) and underlying molecular mechanisms. Methods: HF was induced with 7-day isoproterenol (5 mg/kg daily), confirmed by ejection fraction below 55% after 4 weeks. HF rats received empagliflozin, sacubitril/valsartan, or both for 4 weeks. Parameters measured included hemodynamics, cardiac function, redox status, and histomorphology. Results: Isoproterenol impaired hemodynamics and cardiac function, increased oxidative damage, and altered cardiac structure. All treatments were cardioprotective; however, combined empagliflozin and sacubitril/valsartan therapy had the most pronounced effect. Conclusion: Combined empagliflozin and sacubitril/valsartan showed superior cardioprotection in HF, primarily by enhancing antioxidative effects. These findings support early use of both drugs in HF treatment. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.

Purpose: The idea behind this study was to assess the effects of empagliflozin and sacubitril/valsartan and their combination on isoproterenol-induced heart failure (HF) and underlying molecular mechanisms. Methods: HF was induced with 7-day isoproterenol (5 mg/kg daily), confirmed by ejection fraction below 55% after 4 weeks. HF rats received empagliflozin, sacubitril/valsartan, or both for 4 weeks. Parameters measured included hemodynamics, cardiac function, redox status, and histomorphology. Results: Isoproterenol impaired hemodynamics and cardiac function, increased oxidative damage, and altered cardiac structure. All treatments were cardioprotective; however, combined empagliflozin and sacubitril/valsartan therapy had the most pronounced effect. Conclusion: Combined empagliflozin and sacubitril/valsartan showed superior cardioprotection in HF, primarily by enhancing antioxidative effects. These findings support early use of both drugs in HF treatment. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.

Background/Aim: Hyperhomocysteinaemia is linked to higher level of acetylcholinesterase (AChE) in brain, but there is insufficient information on influence of homocysteine (Hcy) and gasotransmitters on cardiac AChE. Thus, the aim of this study was to evaluate the influence of certain gasotransmitter inhibitors in Hcy-induced changes on rat cardiac AChE activity. Methods: Research was performed on 72 male Wistar albino rats distributed into 6 groups: 1) Control group - saline (1 ml 0.9% NaCl ip); 2) DL-Hcy (8 mmol/kg ip DL homocysteine (DL-Hcy); 3) L-NAME (10 mg/kg ip Nω-Nitro-L-arginine methyl ester (L-NAME), inhibitor of NO production); 4) DL-PAG (50 mg/kg ip DL-propar- gylglycine (DL-PAG), inhibitor of H2S production); 5) DL-Hcy+L-NAME (8 mmol/ kg ip DL-Hcy + 10 mg/kg ip L-NAME); and 6) DL-Hcy+DL-PAG (8 mmol/kg ip DL-Hcy + 50 mg/kg ip DL-PAG). All tested substances were administered in a single dose, intraperitoneally, 60 minutes before animals’ sacrifice. AChE activity was measured in the rats’ cardiac tissue homogenate. Results: Administration of Hcy and L-NAME induced significant decrease in AChE activity compared with control condition. Administration of DL-PAG, DL-Hcy+L- NAME and DL-Hcy+DL-PAG did not change AChE activity compared with the control group. Conclusion: The effects of acute Hcy administration on the cardiac AChE activity are partially mediated via interaction with tested gasotransmitters. © 2019, Faculty of Medicine, University of Banja Luka. All rights reserved.