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Effect of doxorubicin on selected mice microRNAs
Dugasová, Lucia ; Matoušková, Petra (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Lucia Dugasová Supervisor: doc. Ing. Petra Matošková Ph.D. Title of diploma thesis: Effect of doxorubicin on selected mice microRNAs Doxorubicin (DOX) belongs to the anthracycline antibiotics used by patients suffering from cancer. Its undesirable effect is cardiotoxicity. Prognostic of cardiotoxicity depends on its early detection, and therefore many studies examine the properties of microRNAs that could be appropriate biomarkers for heart failure in the future. MicroRNAs are involved in almost all processes in the human body, in development, differentiation, proliferation and apoptosis. They are also located in the extracellular space, they are stable and have many other positive properties. My diploma thesis is focused on monitoring changes in microRNA levels that can occur in heart damage by doxorubicin. The cardiac tissues and plasma of mice treated with doxorubicin were used as samples and compared with control samples. Samples were processed and evaluated by real-time quantitative PCR (qPCR). A statistically significant increase in expression in heart tissue occurred only in miR-34a and decrease in miR-205 level. Plasma mice samples showed a statistically significant increase in...
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Study of the cytotoxicity of selected chemotherapeutics for the treatment of leukemia in human tumor cell lines.
Štorkánová, Jesika ; Novotná, Eva (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Jesika Štorkánová Supervisor: RNDr. Eva Novotná, Ph.D. Title of diploma thesis: Study of the cytotoxicity of selected chemotherapeutics for the treatment of leukemia in human tumor cell lines Leukemia represents a diverse group of malignant diseases with a hematopoietic disorder with different prognoses. As the incidence of patients with leukemia is increasing, is an effort to establish the treatment that will lead to successful therapy. One of the basic approaches to the treatment of leukemias is chemotherapy. Today it is known that the effectiveness of chemotherapy is influenced by a number of factors which can significantly affect the treatment strategy and thus decide on the outcome of the treatment itself. An important approach in chemotherapy is the selection of cytostatics with maximum efficacy for oncological disease and elimination cytostatics to which the cells are resistant based on the findings in in vitro conditions. The aim of this diploma thesis was to determine the inhibitory effects of in vitro selected chemotherapeutics in cell tumor lines. For determine the inhibitory effect, HCT116, HepG2 and HL-60 cell lines were selected using a colorimetric method based on the...
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Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method
Šinaľová, Lucia ; Hofman, Jakub (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucia Šinaľová Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method This master thesis focuses on the prediction of tacrine derivatives permeability through blood- brain barrier and their cytotoxicity. We studied tacrine-benzothiazole and tacrine- thiaquinazoline derivates as potential drugs for treatment of Alzheimer's disease. The reason of testing new tacrine derivates was effort to find substances with same effect and lower toxicity, for which was the tacrine discarded from clinical practice. The probable permeability of the studied substances was determined in vitro by the PAMPA method. Based on the permeation coeficient values we have identified that tacrine-benzothiazole derivates A-D (Pe= 8,31- 16,9×10-6 cm/s) and tacrine-thiaquinazoline derivates 1, 3, 4 (Pe= 8,59-14,9×10-6 cm/s) were permeable through blood-brain barrier, tacrine-thiaquinazoline derivate 2 (Pe= 3,79×10-6 cm/s) had uncertain permeability and tacrine-thiaquinazoline derivate 5 (Pe= 2,0×10-6 cm/s) was not permeable. In the pre-clinical evaluation of...
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Effect of anthelmintics on activity of selected biotranformation enzymes in plants
Hanulíková, Markéta ; Raisová Stuchlíková, Lucie (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Markéta Hanulíková Supervisor: RNDr. Lucie Raisová Stuchlíková, Ph.D. Consultant: RNDr. Radka Podlipná, Ph.D. Title of diploma thesis: Effect of anthelminthics on activity of selected biotransformation enzymes Anthelmintics belong between the drugs widly used in veterinary medicine. In the environment, these drugs represent a significant source of pollution with a negative impact on micro-organism and entire ecosystems. The fate of anthelmintics and their effect on plants has not yet been studied sufficiently. The aim of this work was to investigate the effect of two frequently used anthelmintics, fenbendazole (FEN) and ivermectin (IVM) on antioxidant enzymes peroxidase (POX), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione-S-transferase (GST) and superoxide dismutase (SOD) in model plant Arabidospsis thaliana. In this study was used in vitro cell suspension of Arabidospsis thaliana. Enzyme activity was measured spectrophotometrically in samples taken after 8, 24 and 72 hours. At samples exposed to effect of FEN the activity of SOD enzyme increased, on the other hand the activity of GST enzyme decreased. The presence of IVM has an inhibitory effect on GR, GST...
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Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method
Šinaĺová, Lucia ; Hofman, Jakub (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucia Šinaľová Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Testing of the cytotoxicity of potential drugs in the cell lines together with the measurement of their passage through the blood brain barrier by the PAMPA method This master thesis focuses on the prediction of tacrine derivatives permeability through blood- brain barrier and their cytotoxicity. We studied tacrine-benzothiazole and tacrine- thiaquinazoline derivates as potential drugs for treatment of Alzheimer's disease. The reason of testing new tacrine derivates was effort to find substances with same effect and lower toxicity, for which was the tacrine discarded from clinical practice. The probable permeability of the studied substances was determined in vitro by the PAMPA method. Based on the permeation coeficient values we have identified that tacrine-benzothiazole derivates A-D (Pe= 8,31- 16,9×10-6 cm/s) and tacrine-thiaquinazoline derivates 1, 3, 4 (Pe= 8,59-14,9×10-6 cm/s) were permeable through blood-brain barrier, tacrine-thiaquinazoline derivate 2 (Pe= 3,79×10-6 cm/s) had uncertain permeability and tacrine-thiaquinazoline derivate 5 (Pe= 2,0×10-6 cm/s) was not permeable. In the pre-clinical evaluation of...
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Effect of anthelmintics on activity of selected biotranformation enzymes in plants
Hanulíková, Markéta ; Raisová Stuchlíková, Lucie (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Markéta Hanulíková Supervisor: RNDr. Lucie Raisová Stuchlíková, Ph.D. Consultant: RNDr. Radka Podlipná, Ph.D. Title of diploma thesis: Effect of anthelminthics on activity of selected biotransformation enzymes Anthelmintics belong between the drugs widly used in veterinary medicine. In the environment, these drugs represent a significant source of pollution with a negative impact on micro-organism and entire ecosystems. The fate of anthelmintics and their effect on plants has not yet been studied sufficiently. The aim of this work was to investigate the effect of two frequently used anthelmintics, fenbendazole (FEN) and ivermectin (IVM) on antioxidant enzymes peroxidase (POX), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione-S-transferase (GST) and superoxide dismutase (SOD) in model plant Arabidospsis thaliana. In this study was used in vitro cell suspension of Arabidospsis thaliana. Enzyme activity was measured spectrophotometrically in samples taken after 8, 24 and 72 hours. At samples exposed to effect of FEN the activity of SOD enzyme increased, on the other hand the activity of GST enzyme decreased. The presence of IVM has an inhibitory effect on GR, GST...
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Radiosensitization of non-small cell lung cancer cell line using autophagy inhibitor Lys05
Douděrová, Aneta ; Macháček, Miloslav (advisor) ; Jansová, Hana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Aneta Douděrová Supervisor: RNDr. Miloslav Macháček, PhD. Consultants: pplk. doc. PharmDr. Aleš Tichý, PhD. Title of diploma thesis: Radiosensitization of non-small cell lung cancer cell line using autophagy inhibitor Lys05 Nowadays, tumor diseases belong to the world's main causes of death. Research in the area of tumor treatment deals with the development of new methods that improve the health of patients. The aim of my diploma thesis was to find out if the usage of autophagy inhibitors in combination with ionizing radiation (IR) contributed to radiosensitization of non-small cell lung cancer cells H1299. It was based on an assumption that autophagy was a cytoprotective mechanism leading to a cell survival during stress conditions such as IR. In order to examine qualitative changes of H1299 cells pre-treated by the new autophagy inhibitor Lys05 or well known autophagy inhibitor Bafilomycin A1 we used fluorescence microscopy in combination with green staining by LysoSensor green DND-189. The intensity of fluorescence was quantified by flow cytometry. The results have shown that pre-treatment by autophagy inhibitors in combination with IR led to morphological changes of cells and to...
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Co2+ loaded block copolymer micelles: Preparation and their uptake into macrophages
Měrková, Veronika ; Jansová, Hana (advisor) ; Raisová Stuchlíková, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Friedrich Schiller University Jena Faculty of Chemistry and Earth Sciences Institute for Organic and Macromolecular Chemistry Candidate: Veronika Měrková Supervisors: PharmDr. Hana Jansová, Ph.D., Prof. Dr. Felix H. Schacher Title of diploma thesis: Co2+ loaded block copolymer micelles: Preparation and their uptake into macrophages Since lots of patients suffer from post-operative infections resulting in sepsis, there were attempts to modulate immune system response in order to treat this pathological state. Cobalt is a biogenic trace element, however its direct administration may cause immunological reactions. The immune response can be inflammatory or anti- inflammatory mediated by macrophages (MΦ). Both are responsible for specific actions, regarding MΦ activation and cytokine release. The aim of this study was to provoke such response in MΦ and therefore to possibly control the inflammatory process. Nevertheless, free cobalt ions are toxic. In order to find a suitable and safe way of cobalt administration, the triblock terpolymer PEO-b-PAGECOOH-b-PtBGE was synthesized and assembled into micelles in aqueous solution. Eventually the micelles were loaded with cobalt chloride to facilitate the detection in a...
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The impact of selected sesquiterpenes on antioxidant enzymes in HT-29 cell line
Junková, Martina ; Raisová Stuchlíková, Lucie (advisor) ; Jansová, Hana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Martina Junková Tutor: RNDr. Lucie Raisová Stuchlíková, Ph.D. Title: Effect of selected sesquiterpenes on antioxidant enzymes in the HT-29 cell line Colorectal cancer is one of the most common cancer type in Czech republic. The oncological treatment causes frequent side effects, what result in hard accepting by patients. There is also emerging resistance to classical chemotherapy (5-fluorouracil). During searching new alternatives, some promising natural substances became a subject of researches. The subtropical tree Myrica rubra and its extracts contain many biologically active substances, which are studied among others for their anti-cancer and antiproliferative effects. β-caryophyllene (BCP), β-caryophyllenoxid (CAO), α- humulene (HUM), trans-nerolidol (NER) and valencen (Val) belong to main sesquiterpenes in this essential oil Myrica rubra. In our study, effect of essential oil Myrica rubra, HUM and NER, in concentrations of 25 and 50 μg/ml, were examined after a 24-hours incubation of the HT-29 cell line on the activity of antioxidant enzymes, their transcription and amount of proteins. Monitored enzymes were glutathione peroxidase (GPx), glutathione reductase (GR),...
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