Vitamin B complex mitigates cardiac dysfunction in high-methionine diet-induced hyperhomocysteinemia
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01.07.2018 |
Jeremic J.
Nikolic Turnic T.
Zivkovic V.
Jeremic N.
Milosavljevic I.
Srejovic I.
Obrenovic R.
Jancic S.
Rakocevic M.
Matic S.
Djuric D.
Jakovljevic V.
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Clinical and Experimental Pharmacology and Physiology |
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3 |
Ссылка
© 2018 John Wiley & Sons Australia, Ltd This research is designed to test the hypothesis that elevated homocysteine (Hcy) levels in vivo, caused by a deficit in vitamin B complex, promote changes in cardiac function and redox status that lead to heart failure. In order to conduct the study, we used adult male Wistar albino rats (n = 30; 4 weeks old; 100 ± 15 g body weight). Hyperhomocysteinaemia (HHcy) in these animals was achieved by dietary manipulation. For 4 weeks, the animals were fed with a standard rodent chow (control, CF), a diet enriched in methionine with no deficiency in B vitamins (i.e., folic acid, B6 and B12) (HMNV) or a diet enriched in methionine and deficient in B vitamins (HMLV). After 28 days of dietary manipulation, all animals were killed. The rat hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure. We found a negative correlation between elevated serum Hcy and total body and heart weight. The maximum rate of left ventricular pressure development was significantly increased in the HMNV group compared with in the other groups. Systolic left ventricular pressure was significantly changed in all groups. HHcy induces remodelling of the cardiac tissues, as moderate HHcy is associated with more prominent interstitial and perivascular fibrosis. Our results suggest that a high methionine diet without vitamin B complex causes profound negative effects associated with HHcy.
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The perfusion of cisplatin and cisplatin structural analogues through the isolated rat heart: The effects on coronary flow and cardiodynamic parameters
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01.01.2018 |
Stojic I.
Jakovljevic V.
Zivkovic V.
Srejovic I.
Nikolic T.
Jeremic J.
Jeremic N.
Djuric D.
Radonjic K.
Labudovic-Borovic M.
Bugarcic Z.
Bogojeski J.
Novokmet S.
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General Physiology and Biophysics |
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0 |
Ссылка
© 2018, Slovak Academy of Sciences. All rights reserved. The therapeutic use of cisplatin for the treatment of solid tumours is associated with organ toxicity. Amongst those, the cardiotoxicity is an occasional but very serious and severe side effect. To prevent or reduce these negative effects, many cisplatin analogues have been synthesized and evaluated in terms of being a less toxic and more effective agent. In present study, we examined the effects of cisplatin and its three analogues in the isolated rat heart to determine whether changes in the structure of the platinum complexes (changing of carrier ligands – ethylenediamine; 1,2-diaminocyclohexane; 2,2’:6’,2’’-terpyridine) can influence their cardiotoxic effects. The results of our research indicate that the introduction of aromatic rings in the structure of the platinum complexes has a negative influence on the heart function. Conversely, the other two examined complexes had less negative effects on heart function compared to cisplatin. Our findings may be of interest for a possible synthetic strategy of introducing a carrier ligand that will exert a less cardiotoxic effect.
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Efficiency of atorvastatin and simvastatin in improving cardiac function during the different degrees of hyperhomocysteinemia
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01.01.2018 |
Nikolic Turnic T.
Jakovljevic V.
Djuric D.
Jeremic N.
Jeremic J.
Milosavljevic I.
Srejovic I.
Selakovic D.
Zivkovic V.
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Canadian Journal of Physiology and Pharmacology |
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1 |
Ссылка
© 2018, Canadian Science Publishing. All rights reserved. The aim of this study was to assess the impact of atorvastatin and simvastatin on myocardial contractility during the different degrees of hyperhomocysteinemia (HHcy) in rats. Study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. Animals were exposed to pharmacology treatment with atorvastatin in dose of 3 mg/kg per day i.p. or simvastatin in dose of 5 mg/kg per day i.p. at the same time every day, according to equivalent therapeutic doses of these statins (10 mg atorvastatin = 20 mg simvastatin). After the dietary manipulation and pharmacological treatment and confirmation of HHcy, all animals were sacrificed, hearts were isolated, and cardiac function was tested according to the Langendorff technique. Size of recovery of maximum rate of left ventricular development (dp/dtmax), minimum rate of left ventricular development (dp/dtmin), systolic left ventricular development, diastolic left ventricular development, heart rate, and coronary flow at the 40, 60, 80, 100, and 120 cmH2O coronary perfusion pressure were measured in state of physiological condition (homocysteine less than 15 μmol/L), mild HHcy, and moderate HHcy. Atorvastatin treatment significantly attenuated homocysteine-induced impairment of myocyte contractility and dominantly decreased dp/dtmax, dp/dtmin, and heart rate and induced greater changes in systolic left ventricular development compared with simvastatin. Treatment with atorvastatin seems able to revert systolic abnormalities and improve contractility during the different degrees of HHcy.
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