[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to estimate the protective effect of N-acetyl- l-cysteine (NAC) against cisplatin-induced cardiotoxicity under conditions of ischemic-reperfusion injury. Wistar albino rats were randomly divided into three groups (n=8): control, cisplatin (5mg/kg/w, i.p., 5 weeks) and cisplatin+NAC group (cisplatin - 5mg/kg/w, i.p. and NAC - 500mg/kg/w, i.p., 5 weeks). Isolated hearts were perfused according to the modified Langendorff technique at constant pressure (70cmH2O). Following cardiodynamic parameters were measured: maximum rate of left ventricular pressure development, minimum rate of left ventricular pressure development, left ventricular systolic pressure (SLVP), left ventricular diastolic pressure and heart rate. The ischemic vasodilation episodes were induced by the complete interruption of coronary inflow for 30, 60 and 120s. The samples of the coronary venous effluent (CVE) were continuously collected during the reperfusion period for determination of coronary flow (CF) rate and oxidative stress markers (H2O2, O2-, NO2- and thiobarbituric acid reactive substances - TBARS).Cisplatin reduced CF, heart rate and overflow (total, maximal and duration of overflow) during reperfusion, and increased SLVP (under basal conditions and after global ischemias). Cisplatin increased levels of H2O2 (under basal conditions), O2- and TBARS (under basal conditions and after ischemia), but decreased NO2- levels (during reperfusion) in CVE, and decreased superoxide dismutase and reduced glutathione in serum. NAC attenuated cisplatin-induced changes of cardiodynamic parameters (except CF under basal conditions) and oxidative stress parameters.Those results suggest that NAC, by decreasing oxidative stress, may be useful in cardioprotection during cisplatin therapy.
Full-text · Article · Dec 2015 · Toxicology Reports
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the role of nitric oxide (NO) in cardiac anaphylaxis regarding changes in coronary reactivity and oxidative status of the mice heart. The animals were divided into two groups: experimental group (CBA, iNOS(-/-) mice) and control group: wild-type mice (CBA/H). The hearts of male mice (n = 24; 6-8 weeks old, body mass 20-25 g, 12 in each experimental group) were excised and retrogradely perfused according to the Langendorff technique at a constant perfusion pressure (70 cm H2O). Cardiac anaphylaxis was elicited by injection of solution (1 mg/1 ml) of ovalbumin into the aortic cannula. For the next 10 min, in intervals of 2 min (0-2, 2-4, 4-6, 6-8, 8-10 min) coronary flow (CF) rates were measured and samples of coronary effluent were collected. Markers of oxidative stress including index of lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS), NO measured in the form of nitrites ([Formula: see text]), superoxide anion radical ([Formula: see text]), and hydrogen peroxide (H2O2) in the coronary venous effluent were assessed spectrophotometrically. After the ovalbumin challenge, CF was significantly lower in the wild mice group. NO and H2O2 release were significantly higher in iNOS(-/-) mice group. TBARS and [Formula: see text] values did not vary significantly between wild and iNOS(-/-) mice groups. Our results indicate that coronary vasoconstriction during cardiac anaphylaxis does not necessarily depend on inducible nitric oxide synthase (iNOS)/NO activity and that iNOS/NO pathway may not be an only influential mediator of redox changes in this model of cardiac anaphylaxis.
Full-text · Article · Dec 2015 · Molecular and Cellular Biochemistry
[Show abstract][Hide abstract] ABSTRACT: The aim of our research was to evaluate the changes in levels of cytokines and redox state parameters in blood and isolated heart of rats subjected to different swimming protocols. Rats were divided into 3 groups: 1) controls, 2) moderately trained rats that during all 12 weeks swam 1 h/day, 5 days/week, and 3) overfrequently trained rats that in 10(th) week swam twice, 11(th) week 3 times, and in 12(th) week 4 times a day for 1 hour. After sacrificing, blood from jugular vein was collected, and the heart excised and perfused on a Langendorff apparatus. Samples of the coronary effluent were collected during coronary autoregulation. Levels of superoxide anion radical (O(2)(-)), hydrogen peroxide (H(2)O(2)), nitric oxide (NO) and thiobarbituric acid reactive substances (TBARS) were measured in plasma and coronary effluent, while reduced glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT) were measured in erythrocytes. Venous blood was also used for interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) determination. Moderate training protocol induced the decrease of TBARS in plasma, while both training protocols induced the decrease of O(2)(-) and H(2)O(2) in coronary effluent. There was no significant difference in levels of cytokines between groups. The results of study add evidence about beneficial effects of moderate-intensity training on blood and cardiac redox and state of rats, and furthermore, shows that exercising frequently, if the intensity stays within moderate range, may not have detrimental effects.
No preview · Article · Nov 2015 · Physiological research / Academia Scientiarum Bohemoslovaca
[Show abstract][Hide abstract] ABSTRACT: The results testify to the fact that CO2 is a powerful inhibitor of reactive oxygen species (ROS) generation by cells (blood phagocytes and alveolar macrophages of 96 people and cells of inner organs and tissue phagocytes (of liver, brain, myocardium, lungs, kidneys, stomach, and skeleton muscles), as well as by mitochondria of the liver of 186 white mice and human tissues. Generation of ROS was determined using various methods with CO2 directly acting on the cells and bioptates and indirectly on the organism as a whole. CO2 in the concentration of 5.1 % (P = 37.5 mmHg), 8.2 % (P = 60.0 mmHg), and 20 % (P = 146.0 mmHg) in a mixture with air (total pressure = 730 mmHg) inhibits the basal ROS generation by phagocytes on the average by 3.52, 5.69, and 10.03 times, respectively (p < 0.05), and the stimulated by corpuscular particles: (a) zymosan by 3.24, 4.43, and 7.95 times; (b)SiO2: by 2.99, 3.24, and 5.76 times (p < 0.05). This is confirmed by the feet that CO2, along with inhibiting the O2 (-) generation by cells of the various organs, including the liver, as a rule, by 2.19-4.7 times, p < 0.01 or <0.001 induces simultaneously a decrease in the O2 (-) generation by mitochondria isolated from the liver (by 1.91-3.2 times, p < 0.001). The mechanism of CO2 influence is realized, in part, by inhibition of NADPH-oxidase activity. Taken into consideration proven role of CO2 in different pathophysiological conditions, (such as endoarteritis, bronchial asthma, and infectious diseases), present findings may be of clinical interest in terms of potential implementation of CO2 donors as adjuvant therapeutics in these diseases.
Full-text · Article · Nov 2015 · Molecular and Cellular Biochemistry
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the effects of chronic NAC administration along with cisplatin on cisplatin-induced cardiotoxicity by means of coronary flow (CF), cardiodynamic parameters, oxidative stress markers and morphological changes in isolated rat heart. Isolated hearts of Wistar albino rats (divided into four groups: control, cisplatin, NAC and cisplatin+NAC group) were perfused according to Langendorff technique at constant coronary perfusion pressure starting at 50 and gradually increased to 65, 80, 95 and 110cm H2O to evaluate cardiodynamic parameters within autoregulation range. Samples of coronary venous effluent (CVE) were collected for determination of CF and biochemical assays, and heart tissue samples for biochemical assays and histopathological examination. Cisplatin treatment decreased CF and heart rate, and increased left ventricular systolic pressure and maximum left ventricular pressure development rate. Cisplatin increased H2O2 and TBARS, but decreased NO2(-) levels in CVE. In tissue samples, cisplatin reduced pathological alterations in myocardium and coronary vessels, with no changes in the amount of total glutathione, as well as in activity of glutathione peroxidase and glutathione reductase. NAC coadministration, by reducing oxidative damage, attenuated cisplatin-induced changes of cardiodynamic and oxidative stress parameters, as well as morphological changes in myocardium and coronary vasculature.
Full-text · Article · Nov 2015 · Toxicology Letters
[Show abstract][Hide abstract] ABSTRACT: Background/Aim. Magnetic resonance imaging (MRI) is a key modality not only for lesion diagnosis, but also to evaluate the extension, type and grade of the tumor. Advanced MRI techniques provide physiologic information that complements the anatomic information available from conventional MM. The aim of this study was to determine whether there is a correlation between apparent diffusion coefficient (ADC) maps of intracranial glial tumors and histopathologic findings and whether ADCs can reliably distinguish low-grade from high-grade gliomas. Methods. This retrospective study included 25 patients with MRI examination up to seven days before surgery, according to the standard protocol with the following sequences: T1WI, T2WI, FLAIR, DWI and post contrast T1WI. Data obtained from DW MRI were presented by measuring the value of ADC. The ADC map was determined by utilizing Diffusion-Perfusion (DP) Tools software. All the patients underwent surgical resection of the tumor. Histological diagnosis of tumors was determined according to the World Health Organization (WHO) classification. The ADC values were compared with the histopathologic findings according to the WHO criteria. Results. The ADC values of astrocytomas grades I (0.000614 +/- 0.000032 mm(2)/s) were significantly higher (< 0.001) than the ADC values of anaplastic astrocytomas (0.000436 +/- 0.000016 mm(2)/s) and the ADC values of globlastomas multiforme (0.000070 +/- 0.000008 mm(2)/s). The ADC values of astrocytomas grades II (0.000530 +/- 0.000114 mm(2)/s) were significantly higher (< 0.001) than the ADC values of anaplastic astrocytomas (0.000436 +/- 0.000016 mm(2)/s) and glioblastomas multiforme (0.000070 +/- 0.000008 mm(2)/s). The ADC values of anaplastic astrocytomas (0.000436 +/- 0.000016 mm(2)/s) were significantly higher (< 0.001) than the ADC values of glioblastomas multiforme (0.000070 +/- 0.000008 mm(2)/s). The ADC values in the cystic part of the tumor for astrocytomas grades I (0.000775 +/- 0.000023 mm(2)/s) were significantly higher (< 0.001) than the ADC values of anaplastic astrocytomas (0.000119 +/- 0.000246 mm(2)/s) and glioblastomas multiforme (0.000076 +/- 0.000004 mm(2)/s). The ADC values astrocytomas grades 11 (0.000511 +/- 0.000421 mm(2)/s) were significantly higher (< 0.001) than the ADC values of globlastomas multiforme (0.000076 +/- 0.000004 mm(2)/8). Concluson. DWI with calculation of ADC maps can be regarded as a reliable useful diagnostic tool, which indirectly reflects the proliferation and malignancy of gliomas. The ADCs maps can both predict the results of histopathological tumor and distinguish between low- and high-grade gliomas, and provide significant information for presurgical planning, treatment and prognosis for patients with high-grade astrocytomas.
Full-text · Article · Oct 2015 · Vojnosanitetski pregled. Military-medical and pharmaceutical review
[Show abstract][Hide abstract] ABSTRACT: For the past 40 years, anabolic-androgenic steroids have been used by a wide variety of athletes with the hope of improving their training, endurance, and performance. The aim of this study was to examine the chronic effects of nandrolone decanoate (20 mg/kg, s.c, Deca-Durabolin DECA(®)) on oxidative stress biomarkers in the hearts of sedentary and exercised rats. The male Wistar albino rats (n = 180, four groups with three subgroups, 15 per subgroup, age 10 weeks, body mass 200-220 g) were sacrificed, and in the collected samples of blood, the following markers of oxidative stress were measured spectrophotometrically: (1) index of lipid peroxidation (measured as TBARS-thiobarbituric acid reactive substances); (2) nitrites (NO2 (-)); (3) hydrogen peroxide (H2O2); (4) superoxide anion radical (O2 (-)), and superoxide dismutase, catalase, and glutathione reductase. The results clearly show that the impact of ND alone, or in combination with physical training in general, is mildly pro-oxidative. The chronic physical training probably induces the protective antioxidant enzyme system , which may be of clinical interest when faced with overdosage of this drug.
[Show abstract][Hide abstract] ABSTRACT: Taking into consideration limited data regarding molecular interactions during and after diving, this investigation was intended to determine the oxidative status of divers before and after scuba diving by monitoring the oxidative status parameters. The prevalence study included a group of 32 male professional police scuba divers, 32 ± 5.1 years old. The examination took place twice: in a resting state before scuba diving and immediately after the dive (to 30 meters for 30 minutes). The oxidative status of the scuba divers was determined by measuring levels of the following oxidative stress markers: the index of lipid peroxidation (measured as TBARS), nitrites (NO2-), superoxide anion radical (O2*-), hydrogen peroxide (H2O2), superoxide dismutase (SOD) and catalase (CAT). Statistically significant increases in levels of NO2- and TBARS were observed after the dive, while there were no statistically relevant changes in levels of O2*-, H2O2, SOD and CAT. Our results have shown that a dive with these characteristics only slightly disturbs redox homeostasis, without serious intermolecular changes that can lead to prominent oxidative stress.
[Show abstract][Hide abstract] 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.
Full-text · Article · Jun 2015 · Cardiovascular Toxicology
[Show abstract][Hide abstract] ABSTRACT: Background Adequate assessment of disease activity in patients with systemic lupus erythematosus (SLE) using disease activity index, evaluating the extent of organ damage and quality of life, contributes to better monitoring, treatment, and improved prognosis in SLE patients. Organ damage element of the index in SLE patients predicts further organ damage and is associated with increased risk of mortality.
Objectives Our aim was to examine the correlation between organ damage and disease activity, quality of life, and severity of fatigue. Risk factors for organ damage in SLE patients were established.
Methods The study enrolled 83 SLE patients with disease duration of over 6 months, hospitalized at the Institute “Niška Banja” in 2012, out of which 6 men (7.2%) and 77 women (92.8%), aged 45.8±9.2 years on the average, with average disease duration of 10.6±7.9 years. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and physician's global assessment, and degree of damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for SLE (SLICC/ACR Damage Index - SDI). Quality of life was assessed based on the standardized Medical Outcome Survey Short Form 36 (SF-36), and severity of fatigue using the Fatigue Severity Scale.
Results Average SDI value was 1.8±1.9 (median 1, min. 0, max. 9), and average SLEDAI was 10.9±7.4. Our results demonstrated that SDI was positively correlated with SLEDAI, global physician's assessment, and severity of fatigue (r=0.359, p=0.001; r=0.357, p=0.001; r=0.296, p=0.007, respectively), being associated as well with poorer quality of life. Univariant analysis demonstrated that age, disease duration (especially if over 10 years- OR 3.368, CI95% 1.01-11.34, p=0.045), high disease activity at global physician's assessment, as well as the use of Azathioprine, were all independent risk factors for organ damage. Use of Chloroquine was an important protective factor regarding organ damage (OR 0.378, CI95% 0.14-0.99, p=0.048). Our results demonstrated that the levels of anti-dsDNA antibodies, anti-nucleosome, anti-C1q antibodies, as well as the level of monocyte chemoattractant protein-1 in the serum and urin, were not predictors of organ damage. Multivariant logistic regression showed that high disease activity at global physician's assessment (OR 31.839, 95CI% 2.33-435.58, p=0.01) and use of Azathioprine (OR 7.256, 95CI% 1.37-5.63, p=0.005) were the strongest predictors of organ damage.
Conclusions Organ damage in SLE patients increases with advancing age and disease duration. The strongest predictors of organ damage are high disease activity at global physician's assessment and use of cytostatic agents. Use of Chloroquine can afford some protection against organ damage.
Disclosure of Interest None declared
No preview · Article · Jun 2015 · Annals of the Rheumatic Diseases
[Show abstract][Hide abstract] 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.
Full-text · Article · Apr 2015 · The Chinese journal of physiology
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine oxidative stress (OS) parameters after testicular torsion/detorsion in adult rats.
In this experimental study, male adult Wistar rats were divided into four groups, each consisting of seven animals: group I-one hour right testicular torsion with subsequent orchiectomy, group II-one hour right testicular torsion followed by detorsion, group III-unilateral right-sided orchiectomy without previous torsion and group IV-control. After 30 days, bilateral orchiectomies were performed in rats with both testes and unilateral orchiectomies in rats with single testicles. Parameters of OS were determined in testicular tissue and in plasma.
Plasma concentrations of advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS) were higher (p<0.05 and p<0.01, respectively), whilst the plasma concentration of the total sulfhydryl (T-SH)-groups was lower (p<0.05) in group I compared to the control group. Group II had higher plasma concentrations of AOPP compared to group IV (p<0.05), as well as significantly increased TBARS and decreased T-SH-group levels compared to groups III (p<0.05 and p<0.01, respectively) and IV (p<0.01, for both parameters). There were significant differences in OS markers between the ipsilateral and contralateral testis, as well as significant correlations among levels of both plasma and tissue markers of OS.
The increase in TBARS levels seen throughout the experimental period indicated that OS development was caused by ischemia/reperfusion in the testicular tissue. The oxidant-antioxidant system of the testicular tissue was altered during torsion as well as detorsion.
Full-text · Article · Apr 2015 · International journal of fertility & sterility
[Show abstract][Hide abstract] 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
− 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.
Full-text · Article · Mar 2015 · Molecular and Cellular Biochemistry
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this study was to compare protective effects of ischemic and potential protective effects of pharmacological preconditioning with omeprazole on isolated rat heart subjected to ischemia/reperfusion.
The hearts of male Wistar albino rats were excised and perfused on a Langendorff apparatus. In control group (CG) after stabilization period, hearts were subjected to global ischemia (perfusion was totally stopped) for 20 minutes and 30 minutes of reperfusion. Hearts of group II (IPC) were submitted to ischemic preconditioning lasting 5 minutes before 20 minutes of ischemia and 30 minutes of reperfusion. In third group (OPC) hearts first underwent preconditioning lasting 5 minutes with 100 μM omeprazole, and then submitted 20 minutes of ischemia and 30 minutes of reperfusion.
Administration of omeprazole before ischemia induction had protective effect on myocardium function recovery especially regarding to values of systolic left ventricular pressure and dp/dt max. Also our findings are that values of coronary flow did not change between OPC and IPC groups in last point of reperfusion.
Based on our results it seems that ischemic preconditioning could be used as first window of protection after ischemic injury especially because all investigated parameters showed continuous trend of recovery of myocardial function. On the other hand, preconditioning with omeprazole induced sudden trend of recovery with positive myocardium protection, although less effective than results obtained with ischemic preconditioning not withstand, we must consider that omeprazole may be used in many clinical circumstances where direct coronary clamping for ischemic preconditioning is not possible.
Full-text · Article · Mar 2015 · Revista Brasileira de Cirurgia Cardiovascular