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Study of the protective properties of the series of novel aroylhydrazone iron chelators against the oxidative stress-induced cardiomyocyte injury
Pravdíková, Kateřina ; Šimůnek, Tomáš (advisor) ; Lenčová, Olga (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Pravdíková Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of the protective properties of the series of novel aroylhydrazone iron chelators against the oxidative stress-induced cardiomyocyte injury. Oxidative stress is an imbalance between oxidants and antioxidants in favor of oxidants. In this process occurs the formation of reactive oxygen species (ROS) via the Haber-Weiss reaction, where a redox-active iron participates as the catalyst. ROS play an important role in the pathogenesis of many diseases, including cardiovascular diseases. After clarifying the role of iron in these processes, attention has focused on iron chelators. They may remove free iron ions, which thus cannot catalyse radical reactions, and prevent further development of oxidative damage to the myocardium. The aim of this work was to study the cardioprotective effects of newly synthesized aroylhydrazone derivatives of iron chelator SIH against the toxic effects of hydrogen peroxide in vitro. Their own toxicities were also examined. H9c2 cell line derived from rat embryonic cardiac myoblasts was used for evaluation of the protective and toxic effects of chelators. The evaluation...
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The study of endoglin and eNOS expression in normocholesterolemic mice
Fuxová, Veronika ; Nachtigal, Petr (advisor) ; Lenčová, Olga (referee)
Veronika Fuxová The study of endoglin and eNOS expression in normocholesterolemic mice Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Background: The aim of this diploma was describe the expression of endoglin and eNOS in the aorta in two strain of mice with different predisposition to atherosclerosis. Methods: We used female normocholesterolemic mice from strain C3H/HEJ and from strain CB57BL/6J, which is more susceptible to atherosclerosis. Both groups of mice were fed with chow diet for 12 weeks. Then we performed biochemical analysis of blood specimen and imunohistochemical analysis of segments of tissue from the aorta. To detect expression of endoglin was used Avidin-Biotin Method (ABC) with DAB visualization, to detect expression of eNOS was used En Vision Method again with DAB visiualization. Results: Biochemical analysis showed increase levels of total cholesterol, VLDL, TG and HDL in the strain C3H/HEJ. The imunohistochemical analyse demonstrated expression of endogline and eNOS in endothel of aorta. The results showed that expression of endogline and eNOS is more significant in strain CB57BL/J6 than in strain C3H/HEJ. Conclusion: The expression of endoglin and eNOS was higher in strain CB57BL/6J, which is more susceptible to atherosclerosis...
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Study of cytoprotective properties of novel oxidative stress-activated aroylhydrazone pro-chelators of iron
Macháček, Miloslav ; Šimůnek, Tomáš (advisor) ; Lenčová, Olga (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Miloslav Macháček Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of cytoprotective properties of novel oxidative stress-activated aroylhydrazone prochelators of iron Oxidative stress plays an important role in many disorders including cardiovascular diseases. Fenton reaction catalysed by intracellular redox-active iron is an important source of highly reactive and toxic hydroxyl radicals. Hence, shielding of free iron ions seems to be an advantageous strategy for prevention of further propagation of oxidative stress and myocardial damage. Results from our laboratory as well as other groups have shown promising cardioprotective effect in vitro as well as in vivo experiments. On the other hand, excessive depletion of iron may result in toxicity to the cells. The aim of this project was therefore to examine new iron prochelators, which chelating activity develops only after activation by reactive oxygen species. Boronyl ester of salicylaldehyde isonicotinoyl hydrazone (BSIH) and its derivate BSIH-PD were examined in vitro for their potential protective properties against toxic reactive oxygen species (ROS). Furthermore, own toxicities of studied compounds...
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Study of the protective properties of the series of novel aroylhydrazone iron chelators against the oxidative stress-induced cardiomyocyte injury
Pravdíková, Kateřina ; Šimůnek, Tomáš (advisor) ; Lenčová, Olga (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Pravdíková Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of the protective properties of the series of novel aroylhydrazone iron chelators against the oxidative stress-induced cardiomyocyte injury. Oxidative stress is an imbalance between oxidants and antioxidants in favor of oxidants. In this process occurs the formation of reactive oxygen species (ROS) via the Haber-Weiss reaction, where a redox-active iron participates as the catalyst. ROS play an important role in the pathogenesis of many diseases, including cardiovascular diseases. After clarifying the role of iron in these processes, attention has focused on iron chelators. They may remove free iron ions, which thus cannot catalyse radical reactions, and prevent further development of oxidative damage to the myocardium. The aim of this work was to study the cardioprotective effects of newly synthesized aroylhydrazone derivatives of iron chelator SIH against the toxic effects of hydrogen peroxide in vitro. Their own toxicities were also examined. H9c2 cell line derived from rat embryonic cardiac myoblasts was used for evaluation of the protective and toxic effects of chelators. The evaluation...
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The use of RNA interference for the modification of DNA topoisomerase II levels in cancer cells and its influence on the antineoplastic effect of anthracyclines.
Klieber, Robin ; Jirkovská, Anna (advisor) ; Lenčová, Olga (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department od Biochemical Sciences Candidate: Bc. Robin Klieber Supervisor: PharmDr. Anna Jirkovská, Ph.D. Title of thesis: The use of RNA interference for the modification of DNA topoisomerase II levels in cancer cells and its influence on the antineoplastic effect of anthracyclines. Topoisomerase II (TOP II) is an enzyme that alters the topological state of the DNA double helix during physiological processes through the formation of transient DNA double strand breaks. Two TOP II isoforms are known: TOP IIα is essential for proper separation of chromosomes in mitotic cells, whereas TOP IIβ is primarily associated with gene transcription. Anthracycline antibiotics (ANT) belong to the group of topoisomerase poisons that stabilize the covalent complex of TOP II and DNA. This prevents the religation of the DNA double strand breaks and thus causes irreversible DNA damage leading to programmed cell death. Although ANTs are frequently administered in various antineoplastic protocols (hematooncological malignancies, hormone-dependent tumors and others), the therapy still possess a high risk of irreversible cardiotoxicity. The mechanism of cardiotoxicity remains unraveled. However, it has been previously discussed that TOP IIβ inhibition could play a...
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Study of the protective properties of the series of novel aroylhydrazone iron chelators against the oxidative stress-induced cardiomyocyte injury
Pravdíková, Kateřina ; Šimůnek, Tomáš (advisor) ; Lenčová, Olga (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Pravdíková Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of the protective properties of the series of novel aroylhydrazone iron chelators against the oxidative stress-induced cardiomyocyte injury. Oxidative stress is an imbalance between oxidants and antioxidants in favor of oxidants. In this process occurs the formation of reactive oxygen species (ROS) via the Haber-Weiss reaction, where a redox-active iron participates as the catalyst. ROS play an important role in the pathogenesis of many diseases, including cardiovascular diseases. After clarifying the role of iron in these processes, attention has focused on iron chelators. They may remove free iron ions, which thus cannot catalyse radical reactions, and prevent further development of oxidative damage to the myocardium. The aim of this work was to study the cardioprotective effects of newly synthesized aroylhydrazone derivatives of iron chelator SIH against the toxic effects of hydrogen peroxide in vitro. Their own toxicities were also examined. H9c2 cell line derived from rat embryonic cardiac myoblasts was used for evaluation of the protective and toxic effects of chelators. The evaluation...
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Study of the protective properties of the series of novel aroylhydrazone iron chelators against the oxidative stress-induced cardiomyocyte injury
Pravdíková, Kateřina ; Šimůnek, Tomáš (advisor) ; Lenčová, Olga (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Kateřina Pravdíková Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of the protective properties of the series of novel aroylhydrazone iron chelators against the oxidative stress-induced cardiomyocyte injury. Oxidative stress is an imbalance between oxidants and antioxidants in favor of oxidants. In this process occurs the formation of reactive oxygen species (ROS) via the Haber-Weiss reaction, where a redox-active iron participates as the catalyst. ROS play an important role in the pathogenesis of many diseases, including cardiovascular diseases. After clarifying the role of iron in these processes, attention has focused on iron chelators. They may remove free iron ions, which thus cannot catalyse radical reactions, and prevent further development of oxidative damage to the myocardium. The aim of this work was to study the cardioprotective effects of newly synthesized aroylhydrazone derivatives of iron chelator SIH against the toxic effects of hydrogen peroxide in vitro. Their own toxicities were also examined. H9c2 cell line derived from rat embryonic cardiac myoblasts was used for evaluation of the protective and toxic effects of chelators. The evaluation...
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Study of cytoprotective properties of novel oxidative stress-activated aroylhydrazone pro-chelators of iron
Macháček, Miloslav ; Šimůnek, Tomáš (advisor) ; Lenčová, Olga (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Miloslav Macháček Supervisor: Doc. PharmDr. Tomáš Šimůnek, Ph.D. Title of diploma thesis: Study of cytoprotective properties of novel oxidative stress-activated aroylhydrazone prochelators of iron Oxidative stress plays an important role in many disorders including cardiovascular diseases. Fenton reaction catalysed by intracellular redox-active iron is an important source of highly reactive and toxic hydroxyl radicals. Hence, shielding of free iron ions seems to be an advantageous strategy for prevention of further propagation of oxidative stress and myocardial damage. Results from our laboratory as well as other groups have shown promising cardioprotective effect in vitro as well as in vivo experiments. On the other hand, excessive depletion of iron may result in toxicity to the cells. The aim of this project was therefore to examine new iron prochelators, which chelating activity develops only after activation by reactive oxygen species. Boronyl ester of salicylaldehyde isonicotinoyl hydrazone (BSIH) and its derivate BSIH-PD were examined in vitro for their potential protective properties against toxic reactive oxygen species (ROS). Furthermore, own toxicities of studied compounds...
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The study of endoglin and eNOS expression in normocholesterolemic mice
Fuxová, Veronika ; Nachtigal, Petr (advisor) ; Lenčová, Olga (referee)
Veronika Fuxová The study of endoglin and eNOS expression in normocholesterolemic mice Diploma thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Background: The aim of this diploma was describe the expression of endoglin and eNOS in the aorta in two strain of mice with different predisposition to atherosclerosis. Methods: We used female normocholesterolemic mice from strain C3H/HEJ and from strain CB57BL/6J, which is more susceptible to atherosclerosis. Both groups of mice were fed with chow diet for 12 weeks. Then we performed biochemical analysis of blood specimen and imunohistochemical analysis of segments of tissue from the aorta. To detect expression of endoglin was used Avidin-Biotin Method (ABC) with DAB visualization, to detect expression of eNOS was used En Vision Method again with DAB visiualization. Results: Biochemical analysis showed increase levels of total cholesterol, VLDL, TG and HDL in the strain C3H/HEJ. The imunohistochemical analyse demonstrated expression of endogline and eNOS in endothel of aorta. The results showed that expression of endogline and eNOS is more significant in strain CB57BL/J6 than in strain C3H/HEJ. Conclusion: The expression of endoglin and eNOS was higher in strain CB57BL/6J, which is more susceptible to atherosclerosis...
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