Vladimir Zivkovic

University of Kragujevac, Krabujevac, Central Serbia, Serbia

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Publications (45)54 Total impact

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    ABSTRACT: 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 acute kidney injury; 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 (NO₂⁻), superoxide anion radical (O₂⁻) and hydrogen peroxide (H₂O₂), 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 NO₂⁻ 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, NO₂⁻ and GSH). Whether these changes contribute to the deterioration of renal function in AKI remains to be established.
    The Chinese journal of physiology 04/2015; 58(2). DOI:10.4077/CJP.2015.BAC243 · 1.28 Impact Factor
  • Dalibor Paspalj, Petar Nikic, Milan Savic, Dragan Djuric, Igor Simanic, Vladimir Zivkovic, Nevena Jeremic, Ivan Srejovic, Vladimir Jakovljevic
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    ABSTRACT: Connection between oxidative stress and clinical outcome in acute ischemic stroke (AIS) has been poorly investigated. This study was aimed to assess redox state (through measurement of oxidative stress markers) of patients with acute ischemic stroke during different stages of follow-up period, and to find association between values of mentioned markers and clinical outcome. The investigation was conducted on 60 patients (both sexes, aged 75.90 ± 7.37 years) who were recruited in intensive care units at the Special Hospital for Cerebrovascular Diseases "Sveti Sava," Belgrade. After verification of AIS, patients were followed up in four interval of time: (1) at admission, (2) within 24 h after AIS, (3) within 72 h after AIS, and (4) 7 days after AIS. At these points of time, blood samples were taken for determination of oxidative stress parameters [index of lipid peroxidation (measured as TBARS), nitric oxide (NO) in the form of nitrite ([Formula: see text]), superoxide anion radical ([Formula: see text]), hydrogen peroxide (H2O2)], and enzymes of antioxidant defense system [superoxide dismutase (SOD) and catalase (CAT)] using spectrophotometer. Present study provides new insights into redox homeostasis during ischemic stroke which may be of interest in elucidation of molecular mechanisms involved in this life-threatening condition. Particular contribution of obtained results could be examination of connection between redox disruption and clinical outcome in these patients. In that sense, our finding have pointed out that [Formula: see text] and NO can serve as the most relevant adjuvant biomarkers to monitor disease progression and evaluate therapies.
    Molecular and Cellular Biochemistry 04/2015; DOI:10.1007/s11010-015-2425-z · 2.39 Impact Factor
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    ABSTRACT: In light of the limited data concerning the role of N-methyl-D-aspartate (NMDA) receptors in cardiac function, the aim of the present study was to determine the role of NMDA receptors in cardiac function, as well as the possible role played by the oxidative stress induced by the overstimulation of NMDA receptors in isolated rat heart. The hearts of male, Wistar albino rats (n = 24, 12 in each experimental group, BM 180-200 g) were retrogradely perfused at a constant perfusion pressure (70 cm H2O), using the Langendorff technique, and cardiodynamic parameters were determined during the subsequent administration of DL-homocysteine thiolactone (DL-Hcy TLHC) alone, the combination of DL-Hcy TLHC and dizocilpine (MK-801), and MK-801 alone. In the second experimental group, the order of the administration of each of the substances was reversed. The oxidative stress biomarkers, including thiobarbituric acid reactive substances (TBARS), NO2 (-), O2 (-) and H2O2, were each determined spectrophotometrically. DL-Hcy TLHC and MK-801 depressed cardiac function. DL-Hcy TLHC decreased oxidative stress, a finding that contrasted with the results of the experiments in which MK-801 was administered first. The findings of this study were suggestive of the likely role played by NMDA receptors in the regulation of cardiac function and coronary circulation in isolated rat heart.
    Molecular and Cellular Biochemistry 12/2014; 401(1-2). DOI:10.1007/s11010-014-2296-8 · 2.39 Impact Factor
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    ABSTRACT: We have compared the cardiotoxicity of five platinum complexes in a model of isolated rat heart using the Langendorff technique. These effects were assessed via coronary flow (CF) and cardiac functional parameters. cis-Diamminedichloroplatinum(II) (cisplatin, CDDP), dichloro-(1,2-diaminocyclohexane)platinum(II) (Pt((II))DACHCl2), dichloro-(ethylenediamine)platinum(II) (Pt((II))ENCl2), tetrachloro-(1,2-diaminocyclohexane)platinum(IV) (Pt((IV))DACHCl4) and tetrachloro-(ethylenediamine)platinum(IV) (Pt((II))ENCl4) were perfused at increasing concentrations of 10(-8), 10(-7), 10(-6), 10(-5) and 10(-4) M during 30 min. In this paper, we report that cisplatin-induced dose-dependent effects on cardiac contractility and coronary flow both manifested as decrease in cardiac contractile force (dP/dt)max, heart rate and significant reduction in CF. Pt((II))ENCl2, Pt((IV))ENCl2 and Pt((IV))DACHCl4 did induce dose-dependent response only in case of CF. Our results could be also important for better understanding dose-dependent side effects of potential metal-based anticancer drugs.
    Cardiovascular Toxicology 11/2014; DOI:10.1007/s12012-014-9293-8 · 2.06 Impact Factor
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    ABSTRACT: We estimated the influence of acute glucagon applications on 3H-histamine uptake by the isolated guinea-pig heart, during a single 3H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, , and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change 3H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, 3H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of 3H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9–7.38 × 10−8 μM) is significantly lower than the histamine level in the absence of glucagon (10.35–10.45 × 10−8 μM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis.
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    ABSTRACT: The aim of this study was to assess the oxidative stress status in rheumatoid arthritis (RA) by measuring markers of free radical production, systemic activity of disease, and levels of antioxidant. 52 RA patients and 30 healthy controls were included in the study, and clinical examination and investigations were performed and disease activity was assessed. Peripheral blood samples were used for all the assays. We assessed the markers of oxidative stress, including plasma levels of index of lipid peroxidation-thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), superoxide anion radical (O2 (-)), nitric oxide (NO), and superoxide dismutase activity (SOD), catalase activity (CAT) and glutathione levels in erythrocytes. In the RA group, levels of H2O2, O2 (-), and TBARS were significantly higher than in controls (4.08 ± 0.31 vs. 2.39 ± 0.13 nmol/l, p < 0.01; 8.90 ± 1.28 vs. 3.04 ± 0.38 nmol/l, p < 0.01, 3.65 ± 0.55 vs. 1.06 ± 0.17 μmol/l, p < 0.01). RA patients had significantly increased SOD activity compared with healthy controls (2,918.24 ± 477.14 vs. 643.46 ± 200.63UgHbx103, p < 0.001). Patients had significantly higher levels of pro-oxidants (O2 (-), H2O2, and TBARS) compared to controls, despite significantly higher levels of SOD. Significant differences were also observed in serum levels of NO in patients with high-diseases activity. Our findings support an association between oxidative/nitrosative stress and RA. Stronger response in samples with higher diseases activity suggests that oxidative/nitrosative stress markers may be useful in evaluating the progression of RA as well as in elucidating the mechanisms of disease pathogenesis.
    Molecular and Cellular Biochemistry 03/2014; 391(1-2). DOI:10.1007/s11010-014-2006-6 · 2.39 Impact Factor
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    ABSTRACT: Eicosanoids lead to the promotion of inflammation, cause fever and pain and have many other effects. NSAIDs block the action of cyclooxygenase (COX) during the process of converting arachidonic acid into inflammatory mediators, thus reducing the symptoms of inflammation. Investigations focusing on nonselective COX inhibitors, used in high doses, revealed harmful effects on myocardial function. The aim of our study was to assess the effects of two nonselective NSAIDs, diclofenac and ibuprofen, on cardiodynamic parameters, coronary flow and oxidative stress biomarkers in isolated rat hearts. The hearts of male Wistar albino rats were excised and retrogradely perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40–120 cm H2O). The experiments were performed under controlled conditions (Krebs–Henseleit physiological solution). The hearts were perfused with 10 μmol/l diclofenac and 10 μmol/l ibuprofen. The heart function parameters, including the maximum rate of pressure development (dp/dt max), minimum rate of pressure development (dp/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean perfusion pressure (MBP) and heart rate (HR), were continuously registered. Coronary flow (CF) was measured flowmetrically. Oxidative stress markers, including the index of lipid peroxidation measured as TBARS, nitric oxide measured through nitrites (NO2-), superoxide anion radical (O), and hydrogen peroxide (H2O2) in the coronary venous effluent, were assessed spectrophotometrically. Our results showed that diclofenac affected cardiodynamic parameters more significantly than did ibuprofen. Furthermore, the present data indicate that both estimated COX inhibitors do not promote the production of reactive oxygen species.
    Serbian Journal of Experimental and Clinical Research 01/2014; 15(1):11-19. DOI:10.2478/SJECR20140002
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    ABSTRACT: Vibroacoustics, a scientific field that has been intensively studied for the last thirty years, uses the properties of sound waves (infrasound, ultrasound, noise and music) to induce vibrations that, like a sound wave, may have both useful and harmful effects. The aim of this study was to examine the effects of vibroacoustically induced microvibrations on arterial blood pressure and markers of oxidative stress in the blood. The experiments were performed on Wistar male rats that had a 180-200 g body mass and were divided into control and experimental groups (6 rats in each). In the experimental group, microvibrations were induced using the Vitafon vibroacoustic apparatus (Vitafon, St. Petersburg, Russian Federation), which delivers sound waves of varying frequencies by a process called “phoning”. Up to 60 minutes of phoning time was delivered to the kidney and liver using 4 different regimens that included a 5-minute stabilization time; up to four 10-minute phoning regimens, with 5-minute breaks between each single regimen, at a 30 Hz-18000 kHz frequency range;, and 2.8 μm-12.3 μm microwave amplitudes. After the completion of a phoning regimen, animals were sacrificed and the oxidative stress markers were measured in blood samples (O2-, H2O2, nitrites, lipid peroxidation index, superoxide dismutase, catalase, and glutathione) and compared with the values of markers in the control group. Systolic arterial pressure was analyzed after the acute application of up to four different regimens of vibroacoustic microvibrations. Systolic arterial pressure decreased significantly during the administration of the second regimen in comparison to the control group. Systolic arterial pressure returned, almost completely, to the initial value after the administration of the third and fourth regimens. There was no significant change in diastolic arterial pressure after the acute administration of up to four different regimens, although the pressure decreased slightly after the first and second regimens and returned to the initial value during the administration of the third and fourth regimens. Analysis of oxidative stress markers showed a statistically significant change in the catalase level. No statistically significant differences were found in the other oxidative stress markers analyzed. Further research is needed to clarify the physiological effects of low compared to high frequencies of vibroacoustically induced microvibrations and their possible therapeutic significance.
    Serbian Journal of Experimental and Clinical Research 01/2014; 15(2):83-88.
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    ABSTRACT: Despite the widespread clinical use of cyclooxygenase (COX) inhibitors, dilemmas still exist about potential impact of these drugs on cardiovascular system. The present study was aimed to estimate the effects of different COX inhibitors (meloxicam, acetylsalicylic acid [ASA], and SC-560) on oxidative stress in isolated rat heart, with special focus on L-arginine/NO system. The hearts of male Wistar albino rats (total number n = 96, each group 12 rats, 8 weeks old, body mass 180-200 g) were retrogradely perfused according to the Langendorff technique at gradually increased perfusion pressure (40-120 cmH2O). After control experiments the hearts were perfused with the following drugs: 100 μmol/l ASA (Aspirin), alone or in combination with 30 μmol/l L-NAME, 0.3 μmol/l meloxicam (movalis) with or without 30 μmol/l L-NAME, 3 μmol/l meloxicam (alone or in combination with 30 μmol/l L-NAME), 30 μmol/l L-NAME, and administration of 0.25 μmol/l SC-560. In samples of coronary venous effluent the following oxidative stress markers were measured spectrophotometrically: index of lipid peroxidation (measured as thiobarbituric acid reactive substances [TBARS]), superoxide anion radical release (O2 (-)), and hydrogen peroxide (H2O2). While ASA was found to have an adverse influence on redox balance in coronary circulation, and coronary perfusion, meloxicam and SC-560 do not negatively affect the intact model of the heart. Furthermore, all effects were modulated by NOS inhibition. It seems that interaction between COX and L-arginine/NO system truly exists in coronary circulation, and can be one of the possible causes for achieved effects. That means: those effects induced by different inhibitors of COX are modulated by subsequent inhibition of NOS.
    Molecular and Cellular Biochemistry 06/2013; 381(1-2). DOI:10.1007/s11010-013-1712-9 · 2.39 Impact Factor
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    ABSTRACT: Despite worldwide popularity of soccer, there are still insufficient data about the effects of training process on oxidative stress-induced damage, which may occur during chronic exercise. The present study aimed to determine the effects of a six-month training programme on basal redox status of young male soccer players. The study included 26 male soccer players, aged 12-13, who participated in a six-month training programme, and 26 age-matched non-athletes who were not implemented in the training process. Blood samples were collected (before and after six-month training programme) in order to measure the following oxidative stress markers: index of lipid peroxidation (measured as TBARS), nitrites (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) level. After six months, the levels of TBARS and NO2- were significantly increased, while the O2- and H2O2 remained unchanged. On the other hand, SOD and CAT activity increased, while GSH decreased. A carefully prepared training programme could strengthen most components of antioxidant defence systems and, except lipid peroxidation, does not promote oxidative stress in response to regular physical activity. These findings could help in the improvement of training programmes for young athletes.
    Acta Physiologica Hungarica 03/2013; 100(1):64-76. DOI:10.1556/APhysiol.100.2013.1.6 · 0.75 Impact Factor
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    ABSTRACT: Considering the adverse effects of DL-homocysteine thiolactone hydrochloride (DL-Hcy TLHC) on vascular function and the possible role of oxidative stress in these mechanisms, the aim of this study was to assess the influence of DL-Hcy TLHC alone and in combination with specific inhibitors of important gasotransmitters, such as L-NAME, DL-PAG, and PPR IX, on cardiac contractility, coronary flow, and oxidative stress markers in an isolated rat heart. The hearts were retrogradely perfused according to the Langendorff technique at a 70 cm H2O and administered 10 μ M DL-Hcy TLHC alone or in combination with 30 μ M L-NAME, 10 μ M DL-PAG, or 10 μ M PPR IX. The following parameters were measured: dp/dt max, dp/dt min, SLVP, DLVP, MBP, HR, and CF. Oxidative stress markers were measured spectrophotometrically in coronary effluent through TBARS, NO2, O2 (-), and H2O2 concentrations. The administration of DL-Hcy TLHC alone decreased dp/dt max, SLVP, and CF but did not change any oxidative stress parameters. DL-Hcy TLHC with L-NAME decreased CF, O2 (-), H2O2, and TBARS. The administration of DL-Hcy TLHC with DL-PAG significantly increased dp/dt max but decreased DLVP, CF, and TBARS. Administration of DL-Hcy TLHC with PPR IX caused a decrease in dp/dt max, SLVP, HR, CF, and TBARS.
    01/2013; 2013:318471. DOI:10.1155/2013/318471
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    ABSTRACT: Although the relationship between exercise and oxidative stress has been intensively investigated for over 3 decades, there remains a lack of empirical data on exercise-induced oxidative stress in athletes engaged in sporting games, specifically among the population of elite female athletes. Blood samples were taken from female handball players of the Serbian U20 national team at the beginning and at the end of a one-month preparatory training period, as well as immediately before and after acute treadmill exercise. Levels of superoxide anion radical, hydrogen peroxide, nitric oxide and lipid peroxidation were measured in plasma samples while levels of reduced glutathione and the activity of superoxide dismutase and catalase were measured in erythrocytes. Both experimental protocols demonstrated significant increases in plasma levels of hydrogen peroxide and decreases in superoxide dismutase activity in erythrocytes. Despite the increase in plasma levels of hydrogen peroxide after both the treadmill exercise and the one-month training period, the levels of the two antioxidants responsible for eliminating H2O hydrogen peroxide were not significantly different, as may be expected. Moreover, the marker of lipid peroxidation, TBARS, was not significantly increased. These findings suggest that the first line of antioxidative defence was effective in the prevention of oxidative stress among young female handball players.
    Serbian Journal of Experimental and Clinical Research 01/2013; 14(4):161-168. DOI:10.5937/SJECR4515
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    ABSTRACT: Despite the widespread clinical use of cyclooxygenase (COX) inhibitors, dilemmas regarding the potential impact of these drugs on the cardiovascular system persist. To estimate the effects of different COX inhibitors (meloxicam, acetylsalicylic acid [ASA] and SC-560) on cardiac function and coronary flow in isolated rat hearts, with special focus on the L-arginine/nitric oxide system. The hearts of eight-week-old male Wistar albino rats (n=72; 12 rats per group; body mass 180 g to 200 g) were retrogradely perfused according to the Langendorff technique at gradually increased perfusion pressure (40 cmH2O to 120 cmH2O). After control experiments, the hearts were perfused with the following drugs: 100 μM ASA, alone or in combination with 30 μM N(ω)-nitro-L-arginine monomethyl ester (L-NAME), 0.3 μM meloxicam with or without 30 μM L-NAME, 3 μM meloxicam with or without 30 μM L-NAME, 30 μM L-NAME and 0.25 μM SC-560. In the control and experimental groups, the following parameters of heart function were continuously recorded: maximum rate of left ventricular pressure development, minimum rate of left ventricular pressure development, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate and mean blood pressure. Coronary flow was measured flowmetrically. The amount of released NO2 (-) was determined spectrophotometrically in coronary venous effluent. While meloxicam and SC-560 were found to have an adverse influence on cardiac function and coronary perfusion, ASA did not negatively affect the intact model of the heart. It appeared that interaction between COX and the L-arginine/nitric oxide system truly exists in coronary circulation and may explain the causes of the observed effects.
    Experimental and clinical cardiology 01/2013; 18(2):e102-10. · 0.76 Impact Factor
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    ABSTRACT: Despite the worldwide popularity of football, there is still insufficient data on the effects of the training process on the immune system, followed via serum values of cytokines measured during or following constant exercise. This study aims to assess the effects of a six-month programmed physical activity, on activity of inflammatory mediators in young footballers. The study included 26 players, male, aged 12-13 years, who participated in the six-month training program and 26 sedentary boys who are not entering of the previously mentioned program. Blood samples, which measured levels of the inflammatory mediators TNF-α (tumor necrosis factor alpha) and IL-6 (interleukin six) were taken before and after a six-month training programs. Significantly low values of IL-6 serum (34,73±33,23; 12,52±3,35; p=0,000**) were measured, while the concentration of TNF in the serum did not significantly alter after a 6-month training process. The results obtained in this way can be of an invaluable value in the organizing and dosing of physical activities in young football players.