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Defence mechanisms of lancet fluke against effects of anthelmintics
Ballóková, Anna ; Szotáková, Barbora (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Anna Ballóková Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: Defence mechanisms of lancet fluke against effects of anthelmintics Dicroceliosis, helminthosis caused by Dicrocoelium dendriticum (lancet fluke), is worldwide spread infection of small ruminants. The only way of effective control of this parasitosis is in administration of anthelmintics. In lancet fluke, benzimidazole anthelmintic albendazole metabolism via enzymatic sulfoxidation was found but no information about albendazole oxidases is available. The aim of this work was to identify enzymes involved in the metabolism of albendazole in Dicrocoelium dendriticum isolated from naturally infected mouflons (Ovis musimon). To determinate the involved enzymes some of the specific inhibitors were used. The only effective inhibitors used in this work were α-nafthylthiourea and methimazole, specific inhibitors of flavin-containing monooxygenases. Indole-3-carbinole, used as the specific inhibitor of the same enzymatic system, was without any effect. Other inhibitors were used: 3-amino-1,2,4-triazole for catalase, diethyldithiocarbamate and octylamine for cytochrome P450 and salicylohydroxamic acid and...
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The effect of natural compounds on transport by OATP drug transporters
Zemčíková, Lucie ; Trejtnar, František (advisor) ; Mičuda, Stanislav (referee) ; Szotáková, Barbora (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: MSc. Lucie Zemčíková Supervisor: Assoc. Prof. PharmDr. František Trejtnar, CSc. Title of doctoral thesis: The effect of natural compounds on transport by OATP drug transporters OATP membrane transporters belong to carrier proteins responsible for transporting certain drugs (e.g. hypolipidemics from the group of statins) and other xenobiotics across the biological membranes and tissue barriers within the body. These transport proteins play an important role in pharmacokinetic processes such as absorption, distribution and elimination. The potential modulation of their transport function by natural compounds commonly present in plant food or food supplements may result in the changes of the concentration of their substrate (drug) in the cells and body fluids, that may affect the effect and toxicity of these drugs. The aim of this study was to obtain data on the interactions of selected natural compounds with human transporters OATP2B1 and OATP1A2 and their ability to affect drug transport mediated by these transporters. These two OATP transporters are involved in the drug uptake especially in organ barriers important for pharmacokinetics. For the study natural compounds from the group of...
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Detection of epithelial-mesenchymal transition markers (EMT) in cells in vitro
Špaček, Petr ; Szotáková, Barbora (advisor) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Petr Špaček Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Consultant: RNDr. Věra Králová, Ph.D. Title of diploma thesis: Detection of epithelial-mesenchymal transition (EMT) markers in cells in vitro Epithelial-mesenchymal transition (EMT) is a process during which motile mesenchymal-like cells develop from non-motile parent epithelial cells. Physiologically, EMT plays important roles during embryonic development and wound healing. Loss of control over this mechanism can lead to fibrosis and cancer progression. Motile mesenchymal-like cells can pass through the basal lamina, get into the blood vessels and spread to distant tissues. Transition is regulated by EMT biomarkers. The biomarkers comprise wide spectrum of proteins, including cell surface proteins (E-cadherin, N-cadherin), cytoskeletal proteins (vimentin), microRNA (miR 200) and transcription factors (Snail, Twist). In this study, expression of EMT biomarkers was evaluated using RT-PCR and Western blotting. The ability to migrate was assessed using real-time analysis with the x-CELLigence system. Two known triggers of EMT, the StemXVivo™ EMT Inducing Media Supplement (IS) and TGF-β, were compared in human oral cancer cell lines DOK and...
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The impact of selected sesquiterpenes on the activity of antioxidant enzymes in the differentiated Caco-2 cell line
Verešová, Erika ; Svobodová, Hana (advisor) ; Szotáková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Erika Verešová Supervisor: PharmDr. Hana Bártíková, Ph.D. Title of thesis: The impact of selected sesquiterpenes on the activity of antioxidant enzymes in the differentiated Caco-2 cell line The cases of cancer diagnosis rapidly continue to grow across the population. It is a modern trend to buy more and more often a variety of herbal food supplements in order to strengthen or restore human health. Many scientists have been researching Myrica rubra plant for its potential therapeutic effects. In our research we used sesquiterpenes isolated from this plant, in order to determine their effects on the activity levels of antioxidant enzymes in a differentiated Caco-2 cell line derived from intestinal epithelium tumor that have maintained characteristics of healthy cells. Caco-2 cells are being used as a basis for testing of substances and their effects on non-cancerous cells. The cells were incubated for 24 and 48 hours with a concentration 25 µg/ml of tested substances. Essential oil from Myrica rubra and selected individual sesquiterpenes (α- humulene, β-caryophyllene and trans-nerolidol) were chosen to be tested. Of the antioxidant enzymes, we determined the enzymes glutathione-S-transferase,...
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Transport and biotransformation of anthelmintics in susceptible and resistant strains of Barber's pole worm (Haemonchus contortus)
Prchal, Lukáš ; Szotáková, Barbora (advisor) ; Lamka, Jiří (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lukáš Prchal Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: Transport and biotransformation of anthelmintics in susceptible and resistant strains of Barber's pole worm (Haemonchus Contortus) Haemonchosis is a worldwide problem, which endanger breeding of small ruminants. This disease is caused by nematode Barber's pole worm (Haemonchus contortus), which parasites inside stomachs of host animals, causing anaemia and in many cases death. Pharmacotherapy is the most used way to prevent and/or threat animals. The use of benzimidazole anthemintics is very common, but it's failing more and more often because of resistance of parasites to pharmacotherapy. The most common reason of resistance is mutation in the gene for β-tubuline, which is target for benzimidazoles. This research focuses at the other possible mechanism of resistance, which is resistance based on enzymes and metabolism. One of the aims of this thesis was to compare the metabolism of the anthelmintic drug flubendazole in three different strains of H. contortus: the ISE strain (susceptible to common anthelmintics), the BR strain (resistant to benzimidazole anthelmintics) and the WR strain (resistant to all...
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Effect of Synthetic Magnolol Derivatives on Activity of Nuclear Receptors PPARγ and RXRα
Dymáková, Andrea ; Szotáková, Barbora (advisor) ; Trejtnar, František (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences University of Vienna Faculty of Life Sciences Department of Pharmacognosy Candidate: Andrea Dymáková Supervisors: Mag. Simone Latkolik, doc. Ing. Barbora Szotáková, Ph. D. Title of diploma thesis: Effect of Synthetic Magnolol Derivatives on Activity of Nuclear Receptors PPARγ and RXRα The nuclear receptors, peroxisome proliferator-activated receptor γ (PPARγ) and its heterodimerization partner retinoid X receptor α (RXRα) are drug targets in the treatment of diseases like the metabolic syndrome and diabetes mellitus type 2. The effort has been made to develop new agonists for PPARγ to obtain ligands with more favourable properties than currently used drugs (Berger et al. 2002, Berger et al. 2005). Magnolol was previously described as a dual agonist of PPARγ and RXRα (Fakhrudin et al. 2010, Zhang et al. 2011). Based on the bi- aryl structure of magnolol, the effort has been made to design and synthesize linked magnolol dimers. The aim of this thesis was to investigate the agonistic potential of these compounds with respect of the nuclear receptors PPARγ and RXRα in comparison to magnolol. We evaluated the ligand binding properties of the compounds and their functionality as PPARγ agonists in vitro...
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Influence of albendazole on cell proliferation in vitro
Knoppová, Kateřina ; Szotáková, Barbora (advisor) ; Jirkovská, Anna (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Kateřina Knoppová Supervisor: Doc. Ing. Barbora Szotáková, Ph.D. Supervisor specialist: RNDr. Věra Králová, Ph.D. Title of diploma thesis: Influence of albendazole on cell proliferation in vitro Albendazole (ABZ) is a benzimidazole anthelmintic widely used for the treatment of parasitic diseases in man and animals. The mechanism of action is based on inhibition of microtubule polymerization by binding of ABZ to the β-subunit of tubulin in parasites. As a result, it subsequently leads to the disruption of vital functions of the parasite and to its death. After elucidation of this mechanism, ABZ was tested as a potential anticancer agent. It has been shown that it is able to inhibit proliferation of some cancer cell lines. In this study, we examined the effect of ABZ on cell proliferation in vitro. For the purpose of our experiment we used cell lines derived from colorectal carcinoma - SW 480 and SW 620 together with a cell line NCM 460 isolated from normal colonic mucosa. The cells were treated with ABZ in the concentration range of 0.01 - 10 µM for 24, 48 and 72 hours. Cell viability was determined using WST-1 assay and Neutral Red Uptake Test (NRU). ABZ inhibited cell proliferation...
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