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Analysis of oxidative stress in the model of isoprenaline carditoxicity after intravenous administration of rutinCardiovascular
Sedlářová, Lucie ; Filipský, Tomáš (advisor) ; Fikrová, Petra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Lucie Sedlářová Supervisor: PharmDr. Tomáš Filipský, Ph.D. Title of thesis: Analysis of oxidative stress in the model of isoprenaline carditoxicity after intravenous administration of rutin Cardiovascular diseases are the leading cause of mortality in the developed countries. Among the most serious acute forms of ischemic heart disease belongs acute myocardial infarction (AMI), which can be caused by high levels of endogenous catecholamines. Isoprenaline (ISO), a synthetic catecholamine, evokes a pathological state similar to that of AIM, which is accompanied by an increase in both of unbound iron and copper and the consequent formation of hydroxyl radical in Fenton chemistry. Flavonoids are a large group of substances of natural origin, which represent an important component of human diet and are considered to be beneficial for health status. Their effects include free radical scavenging, iron/copper-chelating properties and inhibiting enzymes producing reactive oxygen species. However, several representatives have showed negative pro-oxidative effects as well. The main aim of this thesis was an analysis of oxidative stress in the model of isoprenaline cardiotoxicity...
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Study of interactions of polyfenolic compounds on nuclear receptors
Dubecká, Michaela ; Pávek, Petr (advisor) ; Filipský, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Supervisor: Title of diplova thesis: Mgr. Michaela Dubecká Prof. PharmDr. Petr Pávek, Ph.D. Study of interactions of polyfenolic compounds on nuclear receptors The farnesoid X receptor (FXR) is a receptor of primary bile acids in the liver and intestine. FXR has been shown to be the master transcriptional regulator of several entero-hepatic metabolic pathways with relevance to the pathophysiology of cholestasis, metabolic syndrome and diabetes, fatty liver disease, cholesterol gallstone disease and intestinal inflammation. Furthermore, FXR plays an important role in the gut-liver axis feedbacks regulating lipid and glucose homeostasis. The apical sodium dependent bile acid transporter (ASBT; SLC10A2) is a bile acid transporter localized to the apical surface of the terminal ileal enterocytes. ASBT plays an important role in the reabsorption of bile acids in the ileum. In the liver, the hepatocytes take up the bile acids by the sinusoidal sodium-dependent taurocholate co-transporting polypeptide (NTCP; SLC10A1). ASBT and NTCP are regulated in the ileum and liver through FXR receptor by bile acids to control bile acids pool. In the current study, we analyzed whether anthocyanins or...
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Assessment of chelating properties of 6,7-dihydroxycoumarin
Kolouch, Jan ; Filipský, Tomáš (advisor) ; Rathouská, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Jan Kolouch Consultant: PharmDr. Tomáš Filipský, Ph.D. Title of thesis: Assessment of chelating properties of 6,7-dihydroxycoumarin Iron is an indispensable element in the human body. This element plays irreplaceable role in many metabolic processes, such as transport of oxygen and synthesis of DNA. The essential feature of iron is its ability to transport electrons and facilitation of catalytic reactions. These reactions are realized by redox properties of iron, which naturally occurs at two different oxidation states, i.e. Fe2+ and Fe3+ . Nevertheless, this element can catalyze not only beneficial, but also toxic reactions. One of those is Fenton reaction, which results in the formation of reactive oxygen species that are toxic to the surrounding tissue. In this thesis we have focused on the assessment of chelating properties of 6,7- dihydroxycoumarin (67DHC) at various pH conditions (4.5, 5.5, 6.8 and 7.5) using both competitive and direct UV-Vis spectrophotometry. Further, we have evaluated its reducing activity at pH 4.5 and 5.5. By the analysis of UV-Vis absorption spectra we have found out, that 67DHC chelated Fe2+ ions at pH 5.5, 6.8 and 7.5 at the chelating ratio 2:1...
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Copper reducing effects of flavones
Jeřábková, Markéta ; Karlíčková, Jana (advisor) ; Filipský, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradci Králové Department of Pharmaceutical botanic and ecology Candidate: Mgr. Markéta Jeřábková Consultant: PharmDr. Jana Karlíčková, Ph.D. Title of Thesis: Copper reducing effects of flavones Free radicals are commonly present in our organism, however, in case of their accumulation it could cause many diseases. Copper is an important trace element which is essential for many biological processes. On the other hand, copper can catalyze processes which produce damaging radicals. Flavonoids are polyphenolic compounds with many biological effects. The most important is antioxidant activity which protects us from free radicals. Flavonids can also have a prooxidant effect. This thesis was focused on a detection of the reducing activity of flavones (mosloflavone, luteolin, apigenin, crysin, diosmin, 5-hydroxyflavone, baicalin, baicalein, negletein, apigenin-7-glucoside) at different pH. A reducing activity of surveyed flavones was taken by the methodics of spectrophotometric analysis with the use of a selective indicator of cuprous ionts formed in bathocuproinedisulfonic acid disodium salt at different pH. A reducing activity depends on the structure of flavones and pH environment. From the definition of the relation between the structure of a flavone...
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Stanovení anthokyanidinů jako potenciálních ligandů lidského konstitutivního androstanového receptoru (hCAR) in vitro
Škoricová, Dagmar ; Pávek, Petr (advisor) ; Filipský, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Dagmar Škoricová Supervisors: Doc. PharmDr. Petr Pávek, Ph.D. Title of rigorosum thesis: Investigating of anthocyanidins as the putative ligands of the human constitutive androstane receptor (hCAR) in vitro Anthocyanidins are natural flavonoid compounds occurring in various fruits and berries, which represent an important part of the normal healthy diet. In addition to their doubtless health benefits, recent studies have suggested that flavonoids are able to activate xenosensors and therefore regulate a wide range of xenobiotic enzymes involved in the biotransformation of drugs, which might be associated with the increased risk of drug-food interaction. Human constitutive androstane receptor (hCAR) is a xenosensor and a nuclear receptor, which regulates the activity of various hepatic and extrahepatic biotransformation enzymes, especially from the CYP superfamily. In this thesis we used the molecular biology methods - Gene reporter assay and Two- hybrid assay to examine the ability of 6 diverse anthocyanidins, cyanidin, delphinidin, malvidin, pelargonidin, peonidin and petunidin to activate the hCAR receptor in vitro. We found, that none of the examined anthocyanidins has...
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Copper chelating activity of flavonols
Jeřábková, Markéta ; Karlíčková, Jana (advisor) ; Filipský, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradci Králové Department of Pharmaceutical botanic and ecology Candidate: Markéta Jeřábková Supervisor: PharmDr. Jana Karlíčková, Ph.D. Title of Thesis: Copper chelating activity of flavonols Copper belongs to essential trace elements. It is involved in different biological processses essential for life therefore metabolism disorders of copper can give rise to patological displays. A raised level of loose copper in serum at some diseases arouses a great interest in the "chelating" therapy and the study of new potential chelators. The importance of chelation is based on the maintenance of copper homeostasis and the elimination of its abundance. It serves the intoxication therapy of copper and other heavy metals and the treatment of Wilson's disease. Flavonoids are polyphenolic compounds with antioxidant effects. Flavonoids able to chelate some metal ions through which they reduce the possibility of the production of a hydroxyl radical which decrease the effect of oxidative stress on organism. The possible use of the "chelating" therapy with flavonoids is investigated also at cardiovascular and neurodegenerative diseases, the occurrence of cancer and the inflammation. This diploma thesis was focused on discovering chelating activity of flavonols:...
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Immunohistochemical detection of PECAM-1, endoglin and VCAM-1 in aorta of transgenic mice with high levels of soluble endoglin
Brlicová, Monika ; Rathouská, Jana (advisor) ; Filipský, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Immunohistochemical detection of PECAM-1, endoglin and VCAM-1 in aorta of transgenic mice with high levels of soluble endoglin Rigorous thesis Mgr. Monika Brlicová Consultant of rigorous thesis: PharmDr. Jana Rathouská, Ph.D. Background: We observed an effect of high level of human soluble endoglin (sEng) on an expression of tissue endoglin and adhesion molecules VCAM-1 and PECAM-1 in descendent aortas of experimental animals. Methods: 6 months old female transgenic mice of strain CBAxC5B7BL/6J with high plasma levels of human soluble endoglin (Sol-Eng+ ) and the same types of mice, which show signs of low plasma levels of human soluble endoglin as control mice were used for this rigorous thesis. Both groups were fed by high fat diet for 3 months. After that the levels of total cholesterol in the blood of these animals were biochemically determined and then statistically evaluated. The immunohistochemical method ImmPRESSTM was used for detection of protein expression in aortic sections. Results: Biochemical analysis showed a statistically insignificant difference in total cholesterol levels in both groups. Immunohistochemical analysis ImmPRESSTM showed no differences in the expression of...
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Study of interactions of polyfenolic compounds on nuclear receptors
Dubecká, Michaela ; Pávek, Petr (advisor) ; Filipský, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Supervisor: Title of diplova thesis: Mgr. Michaela Dubecká Prof. PharmDr. Petr Pávek, Ph.D. Study of interactions of polyfenolic compounds on nuclear receptors The farnesoid X receptor (FXR) is a receptor of primary bile acids in the liver and intestine. FXR has been shown to be the master transcriptional regulator of several entero-hepatic metabolic pathways with relevance to the pathophysiology of cholestasis, metabolic syndrome and diabetes, fatty liver disease, cholesterol gallstone disease and intestinal inflammation. Furthermore, FXR plays an important role in the gut-liver axis feedbacks regulating lipid and glucose homeostasis. The apical sodium dependent bile acid transporter (ASBT; SLC10A2) is a bile acid transporter localized to the apical surface of the terminal ileal enterocytes. ASBT plays an important role in the reabsorption of bile acids in the ileum. In the liver, the hepatocytes take up the bile acids by the sinusoidal sodium-dependent taurocholate co-transporting polypeptide (NTCP; SLC10A1). ASBT and NTCP are regulated in the ileum and liver through FXR receptor by bile acids to control bile acids pool. In the current study, we analyzed whether anthocyanins or...
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Immunohistochemical detection of PECAM-1, endoglin and VCAM-1 in aorta of transgenic mice with high levels of soluble endoglin
Brlicová, Monika ; Rathouská, Jana (advisor) ; Filipský, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Immunohistochemical detection of PECAM-1, endoglin and VCAM-1 in aorta of transgenic mice with high levels of soluble endoglin Rigorous thesis Mgr. Monika Brlicová Consultant of rigorous thesis: PharmDr. Jana Rathouská, Ph.D. Background: We observed an effect of high level of human soluble endoglin (sEng) on an expression of tissue endoglin and adhesion molecules VCAM-1 and PECAM-1 in descendent aortas of experimental animals. Methods: 6 months old female transgenic mice of strain CBAxC5B7BL/6J with high plasma levels of human soluble endoglin (Sol-Eng+ ) and the same types of mice, which show signs of low plasma levels of human soluble endoglin as control mice were used for this rigorous thesis. Both groups were fed by high fat diet for 3 months. After that the levels of total cholesterol in the blood of these animals were biochemically determined and then statistically evaluated. The immunohistochemical method ImmPRESSTM was used for detection of protein expression in aortic sections. Results: Biochemical analysis showed a statistically insignificant difference in total cholesterol levels in both groups. Immunohistochemical analysis ImmPRESSTM showed no differences in the expression of...
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