Cisplatin and cisplatin analogues perfusion through isolated rat heart: the effects of acute application on oxidative stress biomarkers

2017 ◽  
Vol 439 (1-2) ◽  
pp. 19-33 ◽  
Author(s):  
Isidora M. Stojic ◽  
Vladimir I. Zivkovic ◽  
Ivan M. Srejovic ◽  
Tamara R. Nikolic ◽  
Nevena S. Jeremic ◽  
...  
2017 ◽  
Vol 95 (11) ◽  
pp. 1327-1334 ◽  
Author(s):  
Ivan Srejovic ◽  
Vladimir Zivkovic ◽  
Tamara Nikolic ◽  
Nevena Jeremic ◽  
Isidora Stojic ◽  
...  

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. NMDA alone 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.


2015 ◽  
Vol 16 (3) ◽  
pp. 193-199
Author(s):  
Sasa Plecevic ◽  
Olga Pechanova ◽  
Andrej Barta ◽  
Aleksandra Vranic ◽  
Jovana Jeremic ◽  
...  

AbstractIncreased activity of the renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development and progression of various cardio-metabolic diseases, such as hypertension, atherosclerosis and heart failure. Aliskiren is the newest antihypertensive drug and the first orally active direct renin inhibitor to become available for clinical use. This study investigated the acute and direct effects of Aliskiren on different parameters of oxidative stress on isolated rat heart. The hearts of male Wistar albino rats (n = 24, 8 per experimental group, age 8 weeks, body mass 180–200 g), were excised and retrogradely perfused according to the Langendorfftechnique at a gradually increasing perfusion pressure (40-120 cmH2O). Markers of oxidative stress (NO2−, TBARS, H2O2 and O2−) were measured spectrophotometrically after perfusion with three different concentrations of Aliskiren (0.1 μM, 1 μM, and 10 μM). The results demonstrated possible dose-dependent cardioprotective properties of Aliskiren, particularly with higher CPP. Lipid peroxidation (TBARS) levels decreased with the highest dose of Aliskiren and higher CPP, and the same trend was observed in nitrite (NO2−) and hydrogen peroxide (H2O2) levels. These findings indicate that the acute effects of Aliskiren do not likely promote the production of reactive oxygen species upon higher pressure with the highest dose. Aliskiren may exert beneficial effects on oxidative stress biomarkers.


2020 ◽  
Vol 11 (1) ◽  
pp. 15-25
Author(s):  
N. S. Govorushkina ◽  
S. B. Bolevich ◽  
V. Jakovlevich ◽  
B. I. Tachieva ◽  
S. S. Bolevich ◽  
...  

N-methyl-D-aspartate (NMDA) receptors belong to the group of inotropic glutamate receptors, which are found in rat cardiomyocytes.Aim. To evaluate the influence of a non-competitive antagonist of NMDA-receptors — МК-801, separately or in combination with glutamate and/or glycine, on cardiodynamic parameters, coronary flow and oxidative stress biomarkers in isolated rat heart.Materials and methods. 40 Wistar albino rats were divided into 4 groups (10 rats per group). Aorta of isolated rat heart was cannulated and perfused retrogradely by Krebs-Henseleit buffer in the Langendorf mode. Group 1 received МК-801 (50 µmol/l), group 2 received МК-801 and glycine (100 µmol/l), group 3 received МК-801 and glutamate (100 µmol/l) and group 4 received МК-801, glutamate and glycine. Parameters of cardiac dynamics and coronary blood flow were registered during the last minute of tested substance infusion (E) and at the point when artery perfusate samples were taken at the end of the control period (C). The difference between two points (C and E) was calculated and expressed in percent with a standard deviation.Results. Group 1 demonstrated the most prominent decrease of peak left ventricle (LV) pressure increase velocity (–47.59 ± 5.65)%, systolic and diastolic LV pressure: (–45.18 ± 4.87)% and (–37.24 ± 5.15)%, respectively and cardiac rate: (–28.63 ± 3.00)%. The most significant decrease of minimal LV pressure increase velocity was observed in group 2: (–47.43 ± 5.68)%, decrease of coronary blood flow — in group 3: (–23.02 ± 2.49)%. The most significant decline of oxidative stress biomarkers — nitrite and hydrogen peroxide — was observed in group 3: (–29.24 ± 2,70)% and (–23.43 ± 3.15)%, respectively; of superoxide anion radical (O2–) — in group 2: (–55.72 ± 6.90)%, of lipid peroxidation index — in group 1: (–35.77 ± 4.49)%.Conclusion. Administration of МК-801 results in a statistically significant decrease of cardiac dynamic parameters and lipid peroxidation index, compared to MK-801 in combination with glutamate and/or glycine.


EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
S Simovic ◽  
J Jeremic ◽  
G Davidovic ◽  
I Srejovic ◽  
S Mitrovic ◽  
...  

Abstract Introduction Amiodarone represents the most widely used antiarrhythmic drug, even though it has been shown that it has negative inotropic and lusitropic effect in healthy hears. On the other hand, dronedarone reduces the risk of recurrent atrial fibrillation, but with increased early mortality related to the worsening of heart failure. However, the mechanisms responsible for these fatal outcomes remain unclear and require further examinations.  Purpose To investigate acute, direct effects of Dronedarone and Amiodarone on cardiac contractility, coronary flow and oxidative stress parameters in isolated rat heart with hypertension. Methods  The present study was carried out on 18 isolated hearts of spontaneously hypertensive Wistar Kyoto male rats (6 weeks old, bodyweight 200 ± 10 g). After isolation, all hearts were retrogradely perfused according to Langendorff technique with a gradually increment of coronary perfusion pressure (CPP from 40 to 120 cm H2O) and randomly divided into 3 groups: Control (n = 6), Amiodarone (n = 6, isolated hearts perfused with Amiodarone in dose of 3 umol), Dronedarone (n = 6, isolated hearts perfused with Dronedarone in dose of 1.8 umol). During ex vivo protocol continuously were registered cardiac contractility parameters and coronary flow, while from collected coronary venous effluent markers of oxidative stress were measured. All hearts were then fixated and stained with Hematoxylin/eosin. Results  Dronedarone severely depressed the function of all cardiodynamic parameters of the heart compared with Amiodarone or Control while Amiodarone intensified the function of the isolated rat heart with hypertension compared to Control (dp/dt max mmHg/s at coronary perfusion pressure 120cmH2O Dronedarone vs. Amiodarone vs. Control 579.733 ± 202.27 vs. 3063.65 ± 467.93 vs. 2682.88 ± 368.75; p < 0.001. dp/dt min mmHg/s 120cmH2O -352.13 ± 204.65 vs. 1960 ± 242.21 vs. -1858.83 ± 118.23; p < 0.001. SLVP mmHg at CPP 120cmH20 27.8 ± 3.46 vs. 98.95 ± 11.78 vs. 71.45 ± 7.56; p < 0.001. DLVP mmHg at CPP 120cmH2O 6.32 ± 0.49 vs. 4.83 ± 0.54 vs. 0.85 ± 0.35; p < 0.001). Acute administration of Dronedarone decreased the level of NO2- and increased the level of H2O2 , while Amiodarone heightens O2- levels (O2- nmol/min g wt at coronary perfusion pressure 120cmH2O Dronedarone vs. Amiodarone vs. Control  28.62 ± 2.54 vs. 77.3 ± 8.86 vs. 31.72 ± 4.56; p < 0.001. H2O2 nmol/min g wt at CPP 120cmH2O 92.56 ± 11.65 vs. 48.63 ± 10.11 vs. 42.84 ± 84; p < 0.001. NO2- nmol/min g wt at CPP 120cmH2O 38.61 ± 4.94 vs.  82.28 ± 5.76 vs.  64.71 ± 3.51; p < 0.001). Pathohistological, structural changes were observed in both, experimental groups. Conclusions  Acute administration of Dronedarone depresses cardiac function in isolated, working rat heart with hypertension, with decreasing the NO2- levels, increasing the level of H2O2 and enhanced structural changes when compared to Amiodarone.


2015 ◽  
Vol 21 (1) ◽  
pp. 13-19
Author(s):  
Kavous Tahmasebi ◽  
Mahvash Jafari ◽  
Abbas Ahmadi ◽  
◽  
◽  
...  

Author(s):  
Jelena Smigic ◽  
Isidora Stojic ◽  
Vladimir Zivkovic ◽  
Ivan Srejovic ◽  
Tamara Nikolic ◽  
...  

Abstract Taken into consideration that molecular and cellular mechanisms involved in cardiotoxicity are still not clear the aim of this study was to compare the production of oxidative stress parameters in the isolated rat heart between animals chronically treated with cisplatin and saline. Th e hearts of male Wistar albino rats (n = 24, 12 per group, age 8 weeks, body mass 250±50 g) were excised and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH2O). We followed the production of superoxide anion radicals, hydrogen peroxide, and nitrites and also index of lipid peroxidation during the changes of coronary perfusion pressure (CPP) (from 40 to 120 cm H2O) in coronary venous effluent. Modifications CPP were performed in order to determined if oxidative stress is involved in coronary endothelium response in conditions of hypoxia (lower than 60 cm H2O) and hyperoxia (higher than 80 cm H2O). Based on the results of this research we can conclude that with enhancement of CPP the values of oxidative stress statistically increased. However, this increment is more prominent in control group as a result of preserved endothelium and its more powerful response to hyperoxia. On the other hand, damaged endothelium of cisplatin-treated animals had weaker response to hyperoxia, and also lower antioxidant capacity.


Sign in / Sign up

Export Citation Format

Share Document