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Effect of selected compounds on the reduction and toxicity of doxorubicine in the tumorous cellular line
Vildová, Lenka ; 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: Mgr. Lenka Vildová Title, Name, Surname of tutor: Doc. RNDr. Lenka Skálová, Ph.D. Title, Name, Surname of tutor-specialist: Mgr. Martina Gavelová, Ph.D. Title of a diploma work: The effect of selected compounds on reduction and toxicity of doxorubicin in cancer cell line. The anthracycline antibiotic doxorubicin is widely used in the treatment of solid and haematologic malignancies, including breast cancer. The major metabolite of doxorubicin is 13-doxorubicinol that has a significantly lower antineoplastic potency compared to the parent drug and has been implicated as a potential mediator of chronic cardiotoxicity. The aim of the present study was to evaluate the effect of inhibitors of carbonyl reductase 1 (CBR1), such as quercitrin, rutin, and menadion, and prospective anticancer agent oracin on reduction and toxicity of doxorubicin in human breast cancer MCF-7 cells. Experiment performed with menadion revealed that CBR1 plays a important role in reduction of doxorubicin in cytosol of MCF-7 cells. The formation of 13-doxorubicinol was inhibited by oracin that acts as a competitive inhibitor of CBR1. The cytotoxic effect of doxorubicin was examined by the...
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Effect of flavonoids on the metabolism of xenobiotics
Smetanová, Anna ; Szotáková, Barbora (advisor) ; Boušová, Iva (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Title, Name, Surname of candidate: Mgr. Anna Smetanová Title, Name, Surname of tutor: Doc. Ing. Barbora Szotáková, Ph.D. Title of a rigorous work: The influence of flavonoids on the metabolism of xenobiotics Flavonoids are wide spread plant secondary metabolites with the protective effect against the cancer. One of the protective mechanisms of action is the modulation of the biotransformation enzymes. Xenobiotics - heterocyclic aromatic amines are presumably carcinogenic compounds generated during the ordinary cooking of meat and fish. The first metabolic step of the heterocyclic aromatic amines is the procarcinogen activation to the active N-hydroxy metabolites by cytochrome P4501A2 (CYP1A2). It would be desirable if the flavonoids in the appropriate manner modulate the enzymatic activity to eliminate the undesirable effects of the heterocyclic aromatic amines. The aim of this study was to investigate the influence of the rutin and quercetin flavonoids and heterocyclic aromatic amines 2-amino-3-methylimidazo[4,5- f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) on CYP1A activity in the cell line LS174T and HCT-8. Rutin, quercetin, IQ and MeIQx were not toxic for cells up...
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The activity of biotransformation enzymes in mouflons with dicrocoeliosis and in healthy mouflons
Urbánková, Marie ; Szotáková, Barbora (advisor) ; Gavelová, Martina (referee)
Charles University Faculty of Pharmacy Department of Biochemical Sciences Hradec Králové, Czech Republic Field: Patobiochemistry and xenobiochemistry Candidate: Mgr. Marie Urbánková Consultant: Ing. Barbora Szotáková, Ph.D. Title: The activity of biotransformation enzymes in mouflons with dicrocoeliosis and in healthy mouflons Abstract In vitro activities of cytochromes P450 (7-alkyl/aryloxyresorufin dealkyl(aryl)ases, testosterone hydroxylase/oxidase, 7-methoxy-4-trifluoromethyl-coumarin demethylase), flavine monooxygenases (toward thiobenzamide), reductases of carbonyl group (toward oracin, 4-pyridine-carboxaldehyde, 1-acenaphthenol, DL-glyceraldehyde, ketoprofene, naloxone, daunorubicin, metyrapone) and cojnugation enzymes (p-nitrophenol-UDP- glukuronosyl transferase, UGT, 1-chloro-2,4-dinitrobenzene glutathione-S-transferase, GST) in old, female mouflons (Ovis musimon, Bovidae), both in healthy ones and those suffered from dicrocoeliosis were studied and compared. This parasitary disease is caused by Dicrocoelium dendriticum. Various methods were used, especially spectrophotometry, spectrofluorimetry, and method based on incubation of enzymes with relative specific substrate followed with HPLC analysis of biotransformation products. The amount of proteins was determined using methods with reduction of...
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Metabolism of anthelmintics in plants
Pavlík, František ; Szotáková, Barbora (advisor) ; Vokřál, Ivan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: František Pavlík Supervisor: Prof. Ing. Barbora Szotáková, Ph.D. Consultant: RNDr. Radka Podlipná, Ph.D. Title of diploma thesis: Metabolism of anthelmintics in plants Anthelmintics enter into environment mainly through excretion of treated animals. They may cause a lot of adverse effects in ecosystem as they can affect non- target animals or they can accumulate in plants. Further, after consumption of these plants by livestock on pastures the resistence of helminths can be induced. Therefore, the present study was designed to find out biotransformation of frequently used anthelmintics flubendazole (FLU), albendazole (ABZ), fenbendazole (FBZ), ivermectine (IVM) and monepantel (MOP) by the common meadow plants harebell (Campanula rotundifolia) and plantain (Plantago lanceolata), which may often come into contact with anthelmintics through the excrements of treated animals. As model systems, suspensions of harebell and plantain cells and in vitro regenerants of plantain were used. There was no toxic effect of anthelmintics for these plants; they were able to metabolize anthelmintics into a wide scale of various compounds. These metabolites were identified by ultrahigh-performance liquid...
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Influence of albendazole on cell proliferation in vitro
Fišerová, 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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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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