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Determination of the Stoichiometric Ratio of Iron Chelators by Job's Method
Staňová, Zuzana ; Mladěnka, Přemysl (advisor) ; Hašková, Pavlína (referee)
in English Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Candidate: Zuzana Staňová, MSc. Consultanat: Přemysl Mladěnka, Ph.D. Title of Thesis: : Determination of the stoichiometric ratio of iron chelators by Job's method Iron is an important biogenic element affecting many biochemical reactions in the body. Its deficiency and excess cause pathophysiological changes in the organism. Excess of iron is very often the result of frequent blood transfusions in the treatment of hematologic diseases. It may also occur in iron metabolism disorders (chronic intoxication). Acute intoxication after ingestion of excessive amounts of iron is life threatening especially in children. Chelators are used to remove excess iron from the body. It is a heterogeneous group of substances capable of binding iron. Standard drug of this group is parenterally administered deferoxamine. Oral chelators (deferiprone, deferasirox) are also currently used. Other indications of these substances are now the subject of research, which investigates their potential benefits in cancer therapy and acute myocardial infarction. The pH changes play an important role in the pathogenesis of both mentioned conditions. In this work, the stoichiometric ratios of complexes of selected...
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The use of xCELLigence in the study of irinotecan effects on the colorectal carcinoma cells in vitro
Vatahová, Lenka ; Szotáková, Barbora (advisor) ; Hašková, Pavlína (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Lenka Vatahová Supervisor: RNDr. Věra Králová, Ph.D. Title of diploma thesis: The use of xCELLigence in the study of effects of irinotecan in colorectal cancer cells Irinotecan is one of the cytostatic drugs, administered either alone or in combination with 5- fluorouracil (5-FU). Its mechanism of action lies in blocking topoisomerase I resulting in a single-threaded irreparable disruption, which is lethal for the cell. In our study, we examined the use of xCELLigence in the study of effects of irinotecan in colorectal cancer cells. xCELigence, which allows tracking of cells in real time was compared with 2 other methods for determination cell viability, specifically with the WST-1 assay and the Brilliant Blue (BB) assay. Experiments were performed on three cell lines derived from colorectal carcinoma- SW 620, SW 480, and HT 29. The cells were treated with irinotecan in concentration ranges from 5 to 100 µg/ml for 24, 48 and 72 hours. We compared the sensitivity of individual methods and found, that the values differed according to the cell lines. In all cells we calculated the IC 50 value at the time of 72 hours of treatment with irinotecan. And while we have shown that the...
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Iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group II
Břečková, Anna ; Mladěnka, Přemysl (advisor) ; Hašková, Pavlína (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Anna Břečková Supervisor: Přemysl Mladěnka, Ph.D. Title of Thesis: Iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group II Iron deficiency and iron overload play important roles in the pathophysiology of certain human diseases. Administration of iron chelators is a suitable therapy in iron overload conditions, especially in cases of hematological diseases treated with blood transfusions. Iron- chelating therapy appears as well as a promising tool for other diseases (acute myocardial infarction, tumor, etc.). Several factors should be considered according to expected indications: 1) oral efficiency, 2) activity in acidic environment, 3) ability to reduce ferric ions to ferrous ions (risk of pro-oxidation). The aim of this thesis was to verify the iron-chelating properties of selected novel chelators from 4-acyl-5-pyrazolone group by use of UV-VIS spectrophotometric methods. From this group, p-terc.butyl- and p-nitroderivatives of the basic structure and the derivatives marked as H2Q3Q and H2QPy, which are double molecules of the basic structure, were chosen. All of the tested substances had some potential to chelate ferrous ions and were also devoid of...
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In vitro study of newly synthesized potential cardioprotective drugs
Liptáková, Lucie ; Hašková, Pavlína (advisor) ; Macháček, Miloslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Liptáková Supervisor: RNDr. Pavlína Hašková, Ph.D. Title of master thesis: In vitro study of newly synthesized potential cardioprotective drugs Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are in an organism generated under normal or pathological conditions. There are antioxidant mechanisms, which protects the organism from their harmful effect. In case of imbalance between ROS/RNS production and antioxidant mechanisms, an oxidative stress is initiated. The oxidative stress is involved in the pathogenesis of many diseases, including cardiovascular desease. In consequence of higher presence of mitochondria and lower presence of antioxidants cardiomyocytes are more sensitive to the oxidative stress. Iron, by catalysing radical's reactions, significantly participates on formation and development of oxidative stress. Elimination of the free iron by iron chelators is one option how to prevent or moderate oxidative stress. The aim of this master theses was to study cardioprotective effect in presence of H2O2 and own toxicity of newly synthetized aroylhydrazone iron chelators (H21, H22, H23, H24, H25 and H26) on rat embryotic cardiomyoblasts H9c2. Protective and toxic...
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Study of Pathobiochemistry of Catecholamine Cardiotoxicity: Role of Free Iron Ions and Their Chelation as a Possibility of Pharmacological Cardioprotec-tion.
Hašková, Pavlína ; Šimůnek, Tomáš (advisor) ; Dršata, Jaroslav (referee) ; Fusek, Josef (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Pavlína HAŠKOVÁ Supervisor: doc. PharmDr. Tomáš ŠIMŮNEK, Ph.D. Title of Doctoral Thesis: Study of pathobiochemistry of catecholamine cardiotoxicity: Role of free iron ions and their chelation as a possibility of pharmacological cardioprotec- tion. Catecholamine cardiotoxicity is known for a long time, but its patho- genesis is still incompletely understood. Although traditionally attributed to excessive β-adrenergic stimulation, there is a hypothesis that the catecholamine- induced cardiac cell damage includes involvement of oxidation products of catecholamines, which may arise due to spontaneous oxidation of catechola- mines under aerobic conditions. Spontaneous oxidation of catecholamines is a sequence of redox reactions leading to the formation of numerous reactive in- termediates, such as o-semiquinones and o-quinones, including aminochromes that are subject to redox cyclization generating reactive oxygen species (ROS). The generated ROS and aminochromes are toxic for cells. In addition, the autooxidation may be catalyzed by transition metals, which suggests that free intracellular iron (Fe) ions - the most abundant transition metal in the body - can promote not only the Haber-Weiss...
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In vitro study of newly synthesized potential cardioprotective drugs
Liptáková, Lucie ; Hašková, Pavlína (advisor) ; Macháček, Miloslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Liptáková Supervisor: RNDr. Pavlína Hašková, Ph.D. Title of master thesis: In vitro study of newly synthesized potential cardioprotective drugs Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are in an organism generated under normal or pathological conditions. There are antioxidant mechanisms, which protects the organism from their harmful effect. In case of imbalance between ROS/RNS production and antioxidant mechanisms, an oxidative stress is initiated. The oxidative stress is involved in the pathogenesis of many diseases, including cardiovascular desease. In consequence of higher presence of mitochondria and lower presence of antioxidants cardiomyocytes are more sensitive to the oxidative stress. Iron, by catalysing radical's reactions, significantly participates on formation and development of oxidative stress. Elimination of the free iron by iron chelators is one option how to prevent or moderate oxidative stress. The aim of this master theses was to study cardioprotective effect in presence of H2O2 and own toxicity of newly synthetized aroylhydrazone iron chelators (H21, H22, H23, H24, H25 and H26) on rat embryotic cardiomyoblasts H9c2. Protective and toxic...
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In vitro study of newly synthesized potential cardioprotective drugs
Liptáková, Lucie ; Hašková, Pavlína (advisor) ; Macháček, Miloslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lucie Liptáková Supervisor: RNDr. Pavlína Hašková, Ph.D. Title of master thesis: In vitro study of newly synthesized potential cardioprotective drugs Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are in an organism generated under normal or pathological conditions. There are antioxidant mechanisms, which protects the organism from their harmful effect. In case of imbalance between ROS/RNS production and antioxidant mechanisms, an oxidative stress is initiated. The oxidative stress is involved in the pathogenesis of many diseases, including cardiovascular desease. In consequence of higher presence of mitochondria and lower presence of antioxidants cardiomyocytes are more sensitive to the oxidative stress. Iron, by catalysing radical's reactions, significantly participates on formation and development of oxidative stress. Elimination of the free iron by iron chelators is one option how to prevent or moderate oxidative stress. The aim of this master theses was to study cardioprotective effect in presence of H2O2 and own toxicity of newly synthetized aroylhydrazone iron chelators (H21, H22, H23, H24, H25 and H26) on rat embryotic cardiomyoblasts H9c2. Protective and toxic...
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