National Repository of Grey Literature 201 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Study of metabolism air pollutants and mutagens 3-nitrobenzanthrone and 2-nitrobenzanthrone
Čechová, Tereza ; Stiborová, Marie (advisor) ; Martínek, Václav (referee)
Nitroaromatic compounds are mutagenic and carcinogenic substances present in environment. Most of nitroaromatic compounds are potent mutagens in bacterial and mammalian systems. They are also carcinogens causing development of tumors, primarily in the liver, lung and mammary glands. 3-Nitrobenzanthrone (3-NBA, 3-nitro-7H-benz [de] anthracene-7-one) is one of the polycyclic aromatic nitro compounds possesing high toxic effects. 3-NBA is an environmental pollutant present in diesel exhaust and was also detected in soil and in rain water. 2-Nitrobenzanthrone (2-NBA, 2-nitro-7H-benz [de] anthracene-7-one) is an isomer 3-NBA, which also occurs as a pollutant in air. Although the 2-NBA is a weakly toxic substance, its high abundance in air could exhibit a high health risk to humans. This thesis investigates the metabolism of 3-NBA and its isomeric derivate, isomer 2 NBA, under anaerobic and aerobic conditions. To study the metabolism of these compounds, microsomal systems isolated from the liver of rats pretreated with Sudanem I, -naphthoflavone, phenobarbital, ethanol and pregnenolon 16-carbonitrile (PCN), the inducers of cytochromes P450 1A, 2B, 2E1 and 3A, were used. We also used mouse models, a control mouse line (wild type WT) and mice with deleted gene of NADPH:CYP reductase in the liver, thus absenting...
A role of demethylases from JARID 1 family proteins in forming splicing complex
Volek, Martin ; Stiborová, Marie (advisor) ; Martínek, Václav (referee)
Pre-mRNA splicing is a process in which introns are removed from pre-mRNA and exons are ligated. Recent studies confirm that 80 % of pre-mRNA splicing takes place cotranscriptionally, while the pre-mRNA is still attached to the RNA polymerase II. Therefore, pre-mRNA splicing occurs in close proximity to the chromatin, which might influence pre-mRNA splicing. Chromatin can be modified by several modifications. One chromatin modification is histone 3 lysin 4 tri-methylation (H3K4me3). This histone modification is found in the promoter-proximal region of genes, which are actively transcribed. The levels of this modification depend on the transcription activity RNA polymerase II. Indirect binding between H3K4me3 and the U2 snRNP particle via chromo- domain protein CHD1 has been proposed. After demethylation of H3K4me3, the role of this histone modification in forming of splicing complex can be possibly explained. Demethylation of H3K4me3 is catalyzed by the demethylase, JARID1C (Jmj domain, ARID domain). cDNA for JARID1C was cloned into a plasmid. After overexpression of JARID1C in HeLa cells, reduced levels of H3K4me3 were observed by Western blot and immunofluorescence. Differences in mobility of snRNP particles in HeLa cells were measured by fluorescence recovery after photobleaching (FRAP). For U2...
Plant alkaloid sanguinarine and its derivatives
Tůmová, Lucie ; Stiborová, Marie (advisor) ; Hýsková, Veronika (referee)
This work is summarizing actual knowledge about sanguinarine and quaternary benzo[c]fenanthridine alkaloids. The quaternary benzo[c]fenanthridine alkaloids were found in roots plants Sanguinaria canadensis and Macleaya cordata. This plants are used in tradicional Chinese medicine for its antimycotic, antibacterial and anti-inflammatory activities since antiquity. Regarding to possibility quaternary benzo[c]fenanthridine alkaloids to induce apoptosis these investigated such as possible agents for cancer treatment. The quaternary benzo[c]fenanthridine alkaloids interact with DNA and proteins. They are able to intercalate to the DNA. The alkaloids can be used like fluorescence DNA probe. Metabolism by sanguinarine and next quaternary benzo[c]fenanthridine alkaloids has not yet completely determinated. The first step sanguinarine detoxication is its conversion to less toxic dihydrosanguinarine. Sanguinarine oxidation is mediated by cytochrome P450 1A1. Key words: Quaternary benzo[c]fenanthridine alkaloids, sanguinarine, apoptosis, intercalate, heterogenous substances, enzymes, cytochrom P450
Activity of cytochromes P450 1A1, 1A2 and 3A4 expressed in eukaryotic and prokaryotic systems
Indra, Radek ; Stiborová, Marie (advisor) ; Mizerovská, Jana (referee)
Cytochromes P450 (CYP) are a superfamily of heme proteins distributed widely throughout nature, involved in metabolism of a broad variety of substrates and catalyzing a variety of interesting chemical reactions. They play a central role in metabolism of chemotherapeutic agents. Several prodrug antitumor agents have been found as CYP substrates. Ellipticine, an alkaloid found in Apocynaceae plants, is an example of such type of pro-drug. Here, we investigate the efficiencies of human recombinant CYPs expressed in eukaryotic and prokaryotic expression systems, namely in SupersomesTM , microsomes isolated from insect cells transfected with baculovirus construct containing cDNA of human CYP1A1, 1A2 and 3A4 with NADPH:CYP reductase or in Bactosomes, the membrane fraction of E. coli transfected with cDNA of the same human CYP enzymes and NADPH:CYP reductase to oxidize their marker substrates and ellipticine. Cytochrome b5, an aditional component of the mixed function oxidase system, which metabolize xenobiotics was also expressed in some of the systems. The results found in this work demonstrate that human CYP1A1, 1A2 or 3A4 expressed in both eukaryotic and procaryotic systems oxidize their marker substrates (EROD for CYP1A1/2, MROD for CYP1A2 and testosterone 6β-hydroxylation for CYP3A4). They also oxidize...
The study of properties of anticancer drugs ellipticine, etoposide and doxorubicin in the forms of nanocarriers
Lengálová, Alžběta ; Stiborová, Marie (advisor) ; Martínková, Markéta (referee)
Currently available anticancer therapies are inadequate and spur demand for improved technologies. Among others, the utilization of nanocarriers for anticancer drug delivery has shown great potential in cancer treatment. Nanocarriers can improve the therapeutic efficiency of the drugs with minimization of the undesirable side effects. To evaluate potential application of this technology, two forms of nanocarriers have been studied: multi-walled carbon nanotubes (MWCNTs) and apoferritin. The aim of this study was to determine, whether given cytostatics (ellipticine, etoposide and doxorubicin) are bound to these nanotransporters and how are they released from them, especially depending on pH. Since the pH of the tumor cells is lower than the pH of healthy cells it would be preferred that the drugs would release from nanocarriers at the lower pH while at the physiological pH the release of the drug would be eliminated. The results found show that ellipticine is actually released from its MWCNT- and apoferrtin-encapsulated form at acidic pH (5.0), while at pH 7.4 its interaction with nanocarriers is stable. Ellipticine released from MWCNT is activated by microsomal enzymes to reactive metabolites (13- hydroxyellipticine and 12-hydroxyellipticine) forming DNA adducts. The results indicate that both...
Chemoenzymatic separation of diastereoisomers of silybin
Purchartová, Kateřina ; Stiborová, Marie (advisor) ; Wimmer, Zdeněk (referee)
Silybin is major component of silymarin isolated from seeds of the milk thistle (Silybum marianum). This compound is widely used in human medicine against liver disorders and as a protectant against a number of hepatotoxins. It also exhibits other interesting activities as anticancer and chemoprotective, dermatoprotective and also hypocholesterolemic effects. Natural silybin is a nearly equimolar mixture of two diastereoisomers, silybin A and silybin B, whose analytical separation is quite feasible, but preparative separation is extremely complicated. The aim of this work was to find suitable method leading to separation of both silybin diastereoisomers. A library of hydrolases (lipases, esterases and proteases) was tested for their diastereoisomeric discrimination of the selective alcoholysis of 23-O-acetylsilybins. Novozym 435 (lipase B from Candida antarctica immobilized on acrylic resin) proved to be the most suitable enzyme for the preparative production of both optically pure silybin A and B by enzymatic hydrolysis. Under the optimized conditions, silybin A was obtained in 42 % yield and 97 % purity while silybin B was obtained in 67 % yield and 99 % purity. Covalent modifications of Novozym 435 (acetylation, succinylation, and hydroxyethylamidation), which should lead to improvement of...
Study of mechanism of action of anticancer drug ellipticine and its metabolism
Vejvodová, Lucie ; Stiborová, Marie (advisor) ; Moserová, Michaela (referee)
This bachelor thesis is aimed to study the mechanisms of action of anticancer drugs, their side effects, their resistance and pharmacokinetics. Anticancer alkaloid ellipticine was chosen as a model for this work. Bachelor thesis describes the metabolism of this substance in organisms and its potential to induce of drug metabolizing enzymes. An antineoplastic alkaloid ellipticine is a prodrug, whose mode of action is based mainly on DNA intercalation, inhibition of topoisomerasa II, and formation of covalent DNA adducts mediated by cytochromes P450 and/or peroxidases in target tissues. A variety cytochromes P450 oxidize ellipticine forming up to five metabolites (7-hydroxyellipticine, 9- hydroxyellipticine, 12-hydroxyellipticine, 13-hydroxyellipticine and ellipticine N2 - oxide). 7- hydroxy- and 9-hydroxyellipticine metabolites are considered to be mainly the detoxication products of ellipticine, while 12-hydroxyellipticine, 13-hydroxyellipticine and ellipticine N2 - oxide are considered to be mainly the activation products of ellipticine. The major ellipticine- derived DNA adducts are generated from these activation metabolites. These adducts were found in cancer cells in culture, such as human breast adenocarcinoma MCF-7 cells, neuroblastoma IMR-32, UKF-NB-3, and UKF-NB-4 cells and glioblastoma...

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See also: similar author names
1 Stiborová, Marie Luisa
1 Stiborová, Markéta
2 Stiborová, Martina
2 Stiborová, Milada
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