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14. Intravenous rutin in rat exacerbates isoprenaline-induced cardiotoxicity likely due to intracellular oxidative stress

Author

Filipský, Tomáš, primary, Říha, Michal, additional, Hašková, Pavlína, additional, Pilařová, Veronika, additional, Nováková, Lucie, additional, Semecký, Vladimír, additional, Vávrová, Jaroslava, additional, Holečková, Magdaléna, additional, Palicka, Vladimir, additional, Šimůnek, Tomáš, additional, Hrdina, Radomír, additional, and Mladěnka, Přemysl, additional

Published
2016
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17. Intravenous rutin in rat exacerbates isoprenaline-induced cardiotoxicity likely due to intracellular oxidative stress.

Author

Filipský, Tomáš, Říha, Michal, Hašková, Pavlína, Pilařová, Veronika, Nováková, Lucie, Semecký, Vladimír, Vávrová, Jaroslava, Holečková, Magdaléna, Palicka, Vladimir, Šimůnek, Tomáš, Hrdina, Radomír, and Mladěnka, Přemysl

Subjects
CATECHOLAMINES, FLAVONOID glycosides, RUTIN, RATS, CARDIOVASCULAR system abnormalities
Abstract

Objectives: Rutin, quercetin-3-O-rutinoside, a natural flavonol glycoside, has shown variousin vitrobenefits with potential use treating human diseases, especially cardiovascular system disorders. Antioxidant properties are assumed to underlie the majority of these benefits. Yet rutin pro-oxidant properties have been reported as well. Our research group has recently shown aggravating effects on isoprenaline (ISO)-induced cardiotoxicity in Wistar:Han rats after 24 hours. Methods: This study was designed to examine in more detail the reasons for the negative effects of rutin (11.5 and 46 mg/kg, i.v.) after administration of ISO (100 mg/kg, s.c.) in rats within 2 hours of continuous experiment and in the H9c2 cardiomyoblast-derived cell line. Results: Like our previous findings, rutin did not (11.5 or 46 mg/kg, i.v.) reduce the ISO-induced mortality within 2 hours although the lower dose significantly reduced cardiac troponin T (cTnT) and partly improved the histological findings. In contrast, the higher dose increased the mortality in comparison with solvent (1.26% w/v sodium bicarbonate). This was not caused by any specific haemodynamic disturbances. It appears to be associated with oxidative stress as rutin enhanced intracellular reactive oxygen species formationin vitroand had the tendency to increase itin vivo. Conclusions: Rutin, likely due to its pro-oxidative effects, can exacerbate catecholamine cardiotoxicity depending on the dose used. [ABSTRACT FROM AUTHOR]

Published
2017
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20. In vitro evaluation of copper-chelating properties of flavonoids

Author

Říha, Michal, primary, Karlíčková, Jana, additional, Filipský, Tomáš, additional, Macáková, Kateřina, additional, Rocha, Liliana, additional, Bovicelli, Paolo, additional, Silvestri, Ilaria Proietti, additional, Saso, Luciano, additional, Jahodář, Luděk, additional, Hrdina, Radomír, additional, and Mladěnka, Přemysl, additional

Published
2014
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23. Hodnocení terapeutického benefitu antidepresiv

Author

Herink, Josef, Hrdina, Radomír, Říhová, Linda, Herink, Josef, Hrdina, Radomír, and Říhová, Linda

Abstract

Fakulta zdravotnických studií, Dokončená práce s úspěšnou obhajobou

Published
2007

24. In vitro platelet antiaggregatory properties of 4-methylcoumarins

Author

Macáková, Kateřina, primary, Řeháková, Zuzana, additional, Mladěnka, Přemysl, additional, Karlíčková, Jana, additional, Filipský, Tomáš, additional, Říha, Michal, additional, Prasad, Ashok K., additional, Parmar, Virinder S., additional, Jahodář, Luděk, additional, Pávek, Petr, additional, Hrdina, Radomír, additional, and Saso, Luciano, additional

Published
2012
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27. In vitro interactions of coumarins with iron

Author

Mladěnka, Přemysl, primary, Macáková, Kateřina, additional, Zatloukalová, Libuše, additional, Řeháková, Zuzana, additional, Singh, Brajendra K., additional, Prasad, Ashok K., additional, Parmar, Virinder S., additional, Jahodář, Luděk, additional, Hrdina, Radomír, additional, and Saso, Luciano, additional

Published
2010
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29. Direct administration of rutin does not protect against catecholamine cardiotoxicity

Author

Mladěnka, Přemysl, primary, Zatloukalová, Libuše, additional, Šimůnek, Tomáš, additional, Bobrovová, Zuzana, additional, Semecký, Vladimír, additional, Nachtigal, Petr, additional, Hašková, Pavlína, additional, Macková, Eliška, additional, Vávrová, Jaroslava, additional, Holečková, Magdaléna, additional, Palicka, Vladimir, additional, and Hrdina, Radomír, additional

Published
2009
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30. The Novel Iron Chelator, 2-Pyridylcarboxaldehyde 2-Thiophenecarboxyl Hydrazone, Reduces Catecholamine-Mediated Myocardial Toxicity

Author

Mladĕnka, Pr̆emysl, primary, Kalinowski, Danuta S., additional, Hašková, Pavlína, additional, Bobrovová, Zuzana, additional, Hrdina, Radomír, additional, Šimůnek, Tomáš, additional, Nachtigal, Petr, additional, Semecký, Vladimír, additional, Vávrová, Jaroslava, additional, Holečková, Magdaléna, additional, Palicka, Vladimir, additional, Mazurová, Yvona, additional, Jansson, Patric J., additional, and Richardson, Des R., additional

Published
2008
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42. Troponins in Experimental Studies

Author

Adamcová, Michaela, primary, Geršl, Vladimír, additional, Macháčková, Jarmila, additional, Hrdina, Radomír, additional, Klimtová, Ivona, additional, Šimůnek, Tomáš, additional, Vávrová, Jaroslava, additional, and Bukač, Josef, additional

Published
2002
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43. Antiplatelet Effects of Flavonoids Mediated by Inhibition of Arachidonic Acid Based Pathway.

Author

Karlíčková, Jana, Říha, Michal, Filipský, Tomáš, Macáková, Kateřina, Hrdina, Radomír, and Mladěnka, Přemysl

Abstract

Flavonoids, important components of human diet, have been claimed to possess a significant antiplatelet potential, in particular due to their effects on the arachidonic acid cascade. Due to variable and incomplete results, this study was aimed at delivering a detailed analysis of the effects of 29 structurally relevant, mainly natural flavonoids on three consecutive steps of the arachidonic acid cascade. Only the isoflavonoids genistein and daidzein were shown to possess a marked cyclooxygenase-1 inhibitory activity, which was higher than that of acetylsalicylic acid using the isolated ovine enzyme, and physiologically relevant, although lower than acetylsalicylic acid in human platelets. None of the tested flavonoids possesses an effect on thromboxane synthase in a clinically achievable concentration. Contrarily, many flavonoids, particularly those possessing an isolated 7-hydroxyl group and/or a 4'-hydroxyl group, acted as antagonists on thromboxane receptors. Interestingly, the substitution of the free 7-hydroxyl group by glucose might not abolish the activity. In conclusion, the consumption of few flavonoids in a diet, particularly of the isoflavonoids genistein and daidzein, may positively influence platelet aggregation. [ABSTRACT FROM AUTHOR]

Published
2016
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44. Anthracycline-Induced Cardiotoxicity

Author

Hrdina, Radomír, primary, Geršl, Vladimír, additional, Klimtová, Ivona, additional, Šimůnek, Tomáš, additional, Macháčková, Jarmila, additional, and Adamcová, Michaela, additional

Published
2000
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48. The role of reactive oxygen and nitrogen species in cellular iron metabolism.

Author

MLADĚNKA, PŘEMYSL, ŠIMŮNEK, TOMÁŠ, HÜBL, MOJMÍR, and HRDINA, RADOMÍR

Subjects
IRON metabolism, REACTIVE oxygen species, NITROGEN, PROTEINS, HOMEOSTASIS
Abstract

The catalytic role of iron in the Haber–Weiss chemistry, which results in propagation of damaging reactive oxygen species (ROS), is well established. In this review, we attempt to summarize the recent evidence showing the reverse: That reactive oxygen and nitrogen species can significantly affect iron metabolism. Their interaction with iron-regulatory proteins (IRPs) seems to be one of the essential mechanisms of influencing iron homeostasis. Iron depletion is known to provoke normal iron uptake via IRPs, superoxide and hydrogen peroxide are supposed to cause unnecessary iron uptake by similar mechanism. Furthermore, ROS are able to release iron from iron-containing molecules. On the contrary, nitric oxide (NO) appears to be involved in cellular defense against the iron-mediated ROS generation probably mainly by inducing iron removal from cells. In addition, NO may attenuate the effect of superoxide by mutual reaction, although the reaction product—peroxynitrite—is capable to produce highly reactive hydroxyl radicals. [ABSTRACT FROM AUTHOR]

Published
2006
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50. New Possibilities of Cardioprotection in Anthracycline Cardiotoxicity

Author

Kollárová, Petra, Štěrba, Martin, Fusek, Josef, and Hrdina, Radomír

Abstract

Title: New possibilities of cardioprotection in anthracycline cardiotoxicity This PhD thesis is a commented collection of 3 published original papers describing experimental research into protective effects of bisdioxopiperazine derivatives, including clinically used drug dexrazoxane (DEX), against chronic anthracycline (ANT) cardiotoxicity. In the first part, selected derivatives of DEX with chemical structure modified on dioxopiperazine cycles were studied. In vitro experiments suggested a loss of cardioprotective potential in all derivatives tested including those with the smallest change in the ring structure. This assumption was later confirmed in head-to-head comparison with DEX in vivo on a chronic ANT cardiotoxicity model in rabbits. The loss of cardioprotective effect did not correlate with iron chelating properties of the derivatives' metabolites, but it showed good association with ability of parent compounds to interact with topoisomerase IIβ (TOP2B). These experiments also confirmed that the in vitro assays used in this study are suitable for prediction of cardioprotective effects of these substances against chronic ANT cardiotoxicity in vivo. The other part focused on compound ICRF-193 which differs to DEX by a single methyl attached to the aliphatic linker. This compound showed higher...

Published
2022

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