scholarly journals The Effects of Cisplatin and Its PT(II) Analogue on Oxidative Stress of Isolated Rat Heart/ Efekti Cisplatine I PT(II) Analoga Cisplatine Na Oksidacioni Stres Izolovanog Srca Pacova

2016 ◽  
Vol 17 (1) ◽  
pp. 15-20
Author(s):  
Isidora Stojic ◽  
Vladimir Zivkovic ◽  
Ivan Srejovic ◽  
Nevena Jeremic ◽  
Vladimir Jakovljevic ◽  
...  

Abstract To date, numerous platinum (II) complexes have been successfully used in the treatment of different types of cancer. Therapeutic platinum complexes are different in terms of their structure, chemical reactivity, solubility, pharmacokinetics and toxicity. The aim of our research was the evaluation of cardiotoxicity of dichloro-(ethylendiamine) platinum (II) in a model of isolated rat heart using the Langedorff technique. Oxidative stress was assessed by determination of superoxide anion radical, hydrogen peroxide, Thiobarbituric Acid Reactive Substances and nitric oxide levels from coronary venous effluent. All reagents were perfused at increasing concentrations from 10-8 to 10-4 M for 30 minutes. In this paper, we report that substances administered at higher doses did not induce dose-dependent effects on oxidative stress markers. The results of this research may be of great interest for future studies in this area. There are many novel platinum compounds that had previously demonstrated antitumour activity, and these types of experiments in our study can assist in the examination of their cardiotoxicity. These results could be helpful for understanding dose-dependent side effects of existing and novel platinum compounds

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.


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.


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.


2013 ◽  
Vol 381 (1-2) ◽  
pp. 313-313
Author(s):  
Nevena Barudzic ◽  
Drenka Turjacanin-Pantelic ◽  
Vladimir Zivkovic ◽  
Dragica Selakovic ◽  
Ivan Srejovic ◽  
...  

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