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Liver slices - model system for studying the effect of sesquiterpenes on detoxifying enzymes
Slavíčková, Zlata ; Szotáková, Barbora (advisor) ; Ambrož, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Zlata Slavíčková Supervisor: prof. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: Liver slices - model system for studying the effect of sesquiterpenes on detoxifying enzymes Sesquiterpenes are naturally occurring substances, mainly in higher plants as secondary metabolites. Together with monoterpenes, represent the main components of plant essential oils. Sesquiterpenes are biologically active compounds, among their biological activities belong anti-inflammatory, anti-carcinogenic, antioxidant, antibacterial and antimycotic effects. The aim of this diploma thesis was to find out the influence of three structurally similar acyclic sesquiterpenes cis-nerolidol, trans-nerolidol, and farnesol on the activity of selected biotransformation enzymes - aldo-keto reductase (AKR1A1, AKR1C9), carbonyl reductase 1 (CBR1), NAD(P)H-quinone oxidoreductase 1 (NQO1), cytochrome P450 (CYP1A1, CYP1A2, CYP2B, CYP3A), sulfotransferase (SULT), glutathione-S-transferase (GST), and UDP-glucuronosyltransferase (UGT) in rat liver. The influence of sesquiterpenes on selected enzymes was studied in precision-cut liver slices. The precision-cut tissue slices were obtained from rat liver (Rattus norvegicus, tribe...
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Effect of albendazole on the activity of selected enzymes in tapeworm Hymenolepis diminuta
Krejzová, Andrea ; Vokřál, Ivan (advisor) ; Szotáková, Barbora (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Andrea Krejzová Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Effect of albendazole on the activity of selected enzymes in tapeworm Hymenolepis diminuta The efficacy of anthelmintics used to treat diseases caused by helminths is not always sufficient, and in some cases, we are directly facing resistance to these drugs. Helminths, including tapeworms, are able to defend against the toxic effect of anthelmintics using several mechanisms. Xenobiotic metabolizing enzymes and transport proteins belong to these mechanisms. When xenobiotic metabolizing enzymes are induced, the efficacy of therapy may be significantly reduced. The effect of xenobiotic metabolizing enzymes on the drug resistance development has been already described in number of helminths. In tapeworms this information is still missing. Main aim of this study was to determine effect of drug albendazole on the activity of selected xenobiotic metabolizing enzymes in rat tapeworm (Hymenolepis diminuta). Tapeworms were incubated with albendazole (1 μM and 10 μM) for 24 hours. Then activities of selected enzymes in cytosol-like, microsome-like and mitochondria-like fractions were determined. This study is focused on...
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Modulation of biotransformation and antioxidant enzymes by selected natural compounds
Lněničková, Kateřina ; Szotáková, Barbora (advisor) ; Anzenbacherová, Eva (referee) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Kateřina LNĚNIČKOVÁ Supervisor: prof. Ing. Barbora SZOTÁKOVÁ, Ph.D. Title of Doctoral Thesis: MODULATION OF BIOTRANSFORMATION AND ANTIOXIDANT ENZYMES BY SELECTED NATURAL COMPOUNDS Public interest in various dietary supplements containing herbs, herbal extracts or isolated active compounds has increased significantly over past decades. Consumption of these supplements increases worldwide and they are often consumed in unreasonably high doses, as they are generally considered as safe. Upon the intake to organism, these compounds are, as other xenobiotics, modified mostly by xenobiotic-metabolizing enzymes and they could influence these enzymes at the same time. Potential modulation of xenobiotic-metabolizing enzymes' activity (induction or inhibition) can seriously affect pharmacokinetics of concomitantly administered drugs. Knowledge of the possible impact of natural compounds on the xenobiotic-metabolizing enzymes is essential for their safe use. The aim of this doctoral thesis was to study the effects of selected herbal extracts and their active chemical constituents on the activity and expression of xenobiotic-metabolizing and antioxidant enzymes. We have focused on the study of effects of...
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Anthelmintic and other xenobiotic biotransformation in helminths and its contribution to resistance development
Prchal, Lukáš ; Szotáková, Barbora (advisor) ; Hrdý, Ivan (referee) ; Kučera, Radim (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Lukáš Prchal Supervisor prof. Ing. Barbora Szotáková, Ph.D. Title of Doctoral Thesis Anthelmintic and other xenobiotic biotransformation in helminths and its contribution to resistance development Parasitic helminths such as tapeworms, flukes or nematodes pose a threat for domestic, farm and wild living animals. Helminths cause significant health problems in animals. Moreover, they cause economical losses to farmers due to production decrease and treatment costs. The treatment with veterinary anthelmintics is still a basic method to fight off helminth infections. However, the long-term use of anthelmintics caused an emergence of resistance to anthelmintics. The increasing incidence of multiresistant strains of many helminth species is the greatest problem. Therefore, research of drug resistance mechanisms became an actual field of study. Increased biotransformation of anthelmintics, transport out of parasite bodies and contact of lower developmental stages with anthelmintics in the environment are some of possible mechanisms that lead to decrease of anthelmintic therapy effectivity and resistance development. The presented thesis focuses on the study of these mechanisms in three helminth...
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Biological activity of antioxidant compounds in monocytes THP-1
Hájek, Jan ; Boušová, Iva (advisor) ; Szotáková, Barbora (referee)
Charles University in Prague University Roma Tre Faculty of Pharmacy in Hradec Králové Department of Biology Department of Biochemical Sciences Candidate: Jan Hájek Supervisor: PharmDr. Iva Boušová, Ph.D. Prof. Sandra Incerpi, Prof. Jens Z. Pedersen Title of diploma thesis: Biological activity of antioxidant compounds in monocytes THP-1 Elaboration of this work is based on the experiments carried out in the Laboratory of Physiology at University Roma Tre in Rome, under the supervision of Prof. Sandra Incerpi. The team of this laboratory studies the antioxidants of different structures and evaluates their ability to prevent the production of reactive oxygen species (ROS). These reactive species are essential for many physiological processes, but they can also have deleterious effects and participate in the development of various diseases. In this work, I dealt with a study of antioxidant properties of different polyphenolic compounds (mosloflavone, negletein, 5,6-dihydroxyflavone, baicalein, gallic acid, and compound 1625) in the cell culture of human monocytes THP-1 and also in the in vitro test. Three different methods were used: intracellular ROS determination (dichlorofluorescein assay), cytotoxicity assay, and electron paramagnetic resonance spectroscopy (EPR). Mosloflavone showed scavenging...
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Induction and inhibition of acenaphthenol dehydrogenase
Štěrbová, Klára ; Skálová, Lenka (advisor) ; Szotáková, Barbora (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Title, Name, Surname of candidate: Klára Štěrbová Title, Name, Surname of tutor: Doc. RNDr. Lenka Skálová, Ph.D. Title of a diploma work: Induction and inhibition of acenaphthenol dehydrogenase Breast cancer belongs to hormone-dependent tumours. Apart from lifetime exposure to estrogens, the volume of female active sex hormones in breast tissue also plays a big part in the development of this disease. One of mechanisms regulating concentration of estrogens in the target tissue at the pre-receptor level is their interconversion from inactive estron to its active form, 17β-estradiol enzymes from the aldo-ketoreduktas 1C (AKR1C) subfamily. On the basis of specific substrates, inductive and inhibitive studies, enzymes involved in the conversion of individual hormones can be characterized. Relatively specific substrate for AKR1C is acenaphthenol (AcNOH). However, due to the fact that in a multi-enzyme model system the involvement of other enzymes in the reaction cannot be excluded, the enzymes which take part in conversion of acenaphthenol labeled "acenaphtenol dehydrogenase" (AND). The Aim of my diploma paper is to spectrofluorimetrically determine the activity of AND in cytosole taken from breast...
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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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The systemic inflammatory response of the organism to Clostridium difficile infection
Plšková, Martina ; Szotáková, Barbora (advisor) ; Kopecký, Otakar (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Martina Plšková Supervisor: prof. Ing. Barbora Szotáková, Ph.D. Title of rigorous thesis: The systemic inflammatory response of the organism to Clostridium difficile infection Clostridium difficile is currently considered to be the major etiological agent of healthcare-associated diarrhoea in the developed countries. CDI (Clostridium difficile infection) is a potentially life threatening disease of increasing incidence. Despite worldwide research of new highly potent drugs, CDI treatment remains a major problem with regard to the high probability of recurrence and treatment resistance. The aim of this thesis is to find out the number of patients with CDI in a given time period and how CDI affects the C-reactive protein (CRP), leukocyte and neutrophil levels. Rapid membrane enzyme immunoassay for the simultaneous detection of C. difficile glutamate dehydrogenase (GHD) antigen and toxins A and B in a single reaction was used. The RT-PCR method was applied to confirm where a positive result for antigen but negative for toxin appeared. The biochemical determination of CRP was performed turbidimetrically. Complete blood count including a differential count was performed using electrical impedance...
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Effect of prenylated flavonoids on biotransformation enzymes in vitro
Pataráková, Paula ; Szotáková, Barbora (advisor) ; Boušová, Iva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Paula Pataráková Supervisor: Prof. Ing. Barbora Szotáková, Ph.D. Title of diploma thesis: Effect of prenylated flavonoids on biotransformation enzymes in vitro Prenylated flavonoids xanthohumol (XH), isoxanthohumol (IXH), 6-prenylnaringenin (6PN) and 8-prenylnaringenin (8PN) are flavanones and chalcones occurring in hops and their characteristic feature is prenyl chain on A ring. As these substances, present in beer and dietary supplements, are foreign compounds for organism, they can affect drug- metabolizing enzymes, including carbonyl reducing enzymes. The aim of our study was to find out, whether XH, IXH, 6PN, and 8PN have any impact on cytosolic carbonyl reductase 1 (CBR1) and aldo-keto reductase 1C subfamily (AKR1C). Viability test revealed that prenylated flavonoids in lower concentrations do not affect or even increase the viability of primary rat hepatocytes, but higher concentrations are toxic. AKR1C activity was increased in 8PN treated hepatocytes, the activity of CBR1 was significantly increased in IXH and 8PN treated samples. An increase in expression of AKR1C3 in IXH and 6PN treated samples, and decrease in XH and 8PN samples was observed. Expression of CBR1 was at the detection...
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Effect of nanoparticles on plant proteome
Matějková, Lenka ; Szotáková, Barbora (advisor) ; Vytlačilová, Jitka (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Lenka Matějková Supervisor: prof. Ing. Barbora Szotáková, Ph.D. Consultant: RNDr. Radka Podlipná, Ph.D. Title of diploma thesis: Effect of nanoparticles on plant proteome The environment is contaminated by increasing amounts of different types of xenobiotics. Nanomaterials are relatively "new" group of pollutants. Effective method used for decontamination of the environment can be phytoremediation which uses higher plants for biotransformation and accumulation of pollutants. The plant is suitable for phytoremediation when it can absorb, metabolize and store contaminants without significant impact on its metabolism. Influence on the function and construction of the plant can be detected at the proteome level. In this work, we observe the effect of copper oxide nanoparticles on plant proteome of Arabidopsis thaliana. The effect of standard copper oxide particles and copper sulfate ions was also studied in one-day and four-day period for comparison. The proteomes were compared and changes were analyzed by software PDQuest. Changes in intensity of protein spots comparing to the control sample correspond to modulation of the amount of different types of plant proteins. This modulation depends on the...
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