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The influence of metabolites and their parent phenolic compounds on blood platelets
Hrubša, Marcel ; Mladěnka, Přemysl (advisor) ; Moťovská, Zuzana (referee) ; Kollár, Peter (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmacology and Toxicology Candidate: Mgr. Marcel Hrubša Supervisor: Prof. PharmDr. Přemysl Mladěnka, Ph.D. Title of dissertation thesis: The influence of metabolites and their parent phenolic compounds on blood platelets Acute cardiovascular events (ACEs), such as stroke and acute coronary syndromes encompassing acute myocardial infarction, are one of the main causes of cardiovascular mortality in the world. Current pharmacotherapy focuses primarily on secondary prevention of their recurrence, where antiplatelet drugs play a key role. These drugs reduce platelet hyperreactivity, which is present in the majority of cardiovascular and metabolic diseases, and significantly decrease the risk of ACEs. However, the palette of currently available drugs faces many issues, such as resistance, high variability in both pharmacokinetics and pharmacodynamics, serious side effects and the route of administration. This thesis firstly briefly summarizes the current knowledge of platelet physiology along with available antiplatelet drugs and their mechanism of action. Second part of the theoretical introduction is dedicated to polyphenolic compounds, as polyphenol-rich diet is associated with many beneficial effects, particularly...
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The evaluation of senescence markers in the H9c2 cell line after cobalt exposure
Rottenbornová, Lucie ; Jirkovský, Eduard (advisor) ; Hrubša, Marcel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Lucie Rottenbornová Supervisor: PharmDr. Eduard Jirkovský, Ph.D. Title of diploma thesis: The evaluation of senescence markers in the H9c2 cell line after cobalt exposure Introduction and aim: Cellular senescence is the response of a cell to a physiological or stressful stimulus. Cobalt is an element that simulates hypoxia under normoxic conditions through hypoxia-inducible factors. One of the factors that can induce cellular senescence is hypoxia. The aim of the work was to evaluate p16INK4a and Ki67 proteins as markers of cell senescence in an H9c2 cell line after exposure to CoCl2. Methods: Cytotoxicity was measured using the MTT assay on the H9c2 cell line after 24 and 48 hours of exposure to CoCl2. Subsequently, relative gene expression of genes associated with hypoxia (HIF1α and BNIP3) and senescence (p16INK4a and Ki67) in H9c2 after exposure to cobalt was investigated using the RT-PCR method. Results: Exposure of H9c2 cells to CoCl2 induced dose- and time-dependent toxicity. After a 24-hour exposure, CoCl2 toxicity was not observed up to a concentration of 100 μM, the IC50 value was 500.5 μM. After 48 hours of exposure, higher toxicity was observed already at 100 μM concentration and...
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The influence of metabolites and their parent phenolic compounds on blood platelets
Hrubša, Marcel ; Mladěnka, Přemysl (advisor) ; Moťovská, Zuzana (referee) ; Kollár, Peter (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmacology and Toxicology Candidate: Mgr. Marcel Hrubša Supervisor: Prof. PharmDr. Přemysl Mladěnka, Ph.D. Title of dissertation thesis: The influence of metabolites and their parent phenolic compounds on blood platelets Acute cardiovascular events (ACEs), such as stroke and acute coronary syndromes encompassing acute myocardial infarction, are one of the main causes of cardiovascular mortality in the world. Current pharmacotherapy focuses primarily on secondary prevention of their recurrence, where antiplatelet drugs play a key role. These drugs reduce platelet hyperreactivity, which is present in the majority of cardiovascular and metabolic diseases, and significantly decrease the risk of ACEs. However, the palette of currently available drugs faces many issues, such as resistance, high variability in both pharmacokinetics and pharmacodynamics, serious side effects and the route of administration. This thesis firstly briefly summarizes the current knowledge of platelet physiology along with available antiplatelet drugs and their mechanism of action. Second part of the theoretical introduction is dedicated to polyphenolic compounds, as polyphenol-rich diet is associated with many beneficial effects, particularly...
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