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Induction of heme oxygenase and biological role of its metabolic products.
Šuk, Jakub ; Muchová, Lucie (advisor) ; Jirsa, Milan (referee) ; Neužil, Jiří (referee)
Heme oxygenase (HMOX) catalyzes first and rate-limiting step in heme degradation. By its action, carbon monoxide (CO), ferrous iron and biliverdin which is subsequently reduced to bilirubin are produced. Before discovery of HMOX reaction mechanism, CO was considered only a toxic waste product without any significant importance for human organism. Bilirubin, marker of liver dysfunction, has been also exposed to similar perception. But results from past decades show that HMOX and its metabolic products play an important role in number of physiological as well as defense against pathophysiological processes. The aim of this thesis was to clarify the role of HMOX and its metabolic products, presumably CO and bilirubin, in vivo and in vitro. We focused on the role of CO in a rat model of lipopolysaccharide-induced cholestasis. We were first to describe tissue distribution and pharmacokinetics of inhaled CO in this animal model and found out that CO inhalation is associated with anti-inflammatory and hepatoprotective effects. In a rat model of ethinylestradiol-induced cholestasis, we demonstrated the anticholestatic effect of HMOX. The induction of HMOX by its substrate heme increased the expression of liver transporters thereby increasing bile flow and simultaneously facilitated effective clearance of...
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Determination of the stoichiometry of the copper complexes with dehydrosilybine A
Klimková, Kateřina ; Mladěnka, Přemysl (advisor) ; Hrdina, Radomír (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Kateřina Klimková Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm. D., Ph.D. Consultant: Assoc. Prof. Kateřina Valentová, Ph.D. Title of Thesis: Determination of the stoichiometry of the copper complexes with dehydrosilybin A Silymarin, the standardized extract of the milk thistle (Silybum marianum), is a widely used approved over-the-counter drug that is recommended for a number of liver diseases. Silymarin contains as one of its components 2,3-dehydrosilybinA, which has an appropriate metal binding site in its structure. In general, flavonolignans, due to their structure, can interact with transition metals in the gastrointestinal tract by forming complexes. This property can be useful for the protection against excessive amounts of metals in the body. The aim of this in vitro study was to analyse the interaction of 2,3-dehydrosilybin A with copper, which plays a crucial role in the organism as a cofactor of many enzymes. Although being an essential element, it can, however, be toxic at elevated levels. Stoichiometry, as one of the most important characteristics of the complex, was determined by UV-Vis spectrophotometry in four (patho)physiological pH conditions (4.5; 5.5; 6.8; 7.5)...
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Determination of the stoichiometry of the copper complexes with dehydrosilybine A
Klimková, Kateřina ; Mladěnka, Přemysl (advisor) ; Hrdina, Radomír (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Kateřina Klimková Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm. D., Ph.D. Consultant: Assoc. Prof. Kateřina Valentová, Ph.D. Title of Thesis: Determination of the stoichiometry of the copper complexes with dehydrosilybin A Silymarin, the standardized extract of the milk thistle (Silybum marianum), is a widely used approved over-the-counter drug that is recommended for a number of liver diseases. Silymarin contains as one of its components 2,3-dehydrosilybinA, which has an appropriate metal binding site in its structure. In general, flavonolignans, due to their structure, can interact with transition metals in the gastrointestinal tract by forming complexes. This property can be useful for the protection against excessive amounts of metals in the body. The aim of this in vitro study was to analyse the interaction of 2,3-dehydrosilybin A with copper, which plays a crucial role in the organism as a cofactor of many enzymes. Although being an essential element, it can, however, be toxic at elevated levels. Stoichiometry, as one of the most important characteristics of the complex, was determined by UV-Vis spectrophotometry in four (patho)physiological pH conditions (4.5; 5.5; 6.8; 7.5)...
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The effect of silymarin, naringin and resveratrol on the liver damage induced by some xenobiotics
Kovaříková, Pavla ; Eybl, Vladislav (advisor) ; Anzenbacherová, Eva (referee) ; Mayer, Otto (referee)
The vast majority of exogenous substances is metabolized in the liver. In the course of the biotransformation, partly biologically non-active products, partly reactive species leading to cell structure injury and even to the liver failure are produced. Oxidative stress plays a significant role in the toxic- and drug-induced liver damage. Endogenous and exogenous antioxidants contribute to equilibrium between the production and the elimination of reactive oxygen species and thus prevent the oxidative stress. In acute experiments in rats we examined the ability of natural antioxidants silymarin, naringin and resveratrol and of synthetic chelator deferipron to protect against liver damage induced by paracetamol, thioacetamide and tamoxifen. The following parameters of oxidative stress were measured in the liver homogenates: level of lipid peroxidation (LP), concentration of reduced glutathione (GSH), activities of glutathione peroxidase (GPx) and of catalase (CAT); in some cases the iron liver content. The following markers of liver damage were measured in serum: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH). Concernig markers of oxidative status, silymarin exerted the most efficient antioxidant properties amelioratig the TAA- and TAM-induced lipid...
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Preparative diastereomeric separation of silybin and its sulfates by RP-HPLC
Kolářová, Petra ; Tesařová, Eva (advisor) ; Kalíková, Květa (referee)
Silymarin is standardized extract isolated from fruits of Milk Thistle plant (Silybum marianum). The principal component of silymarin is silybin. This flavonolignan is mainly responsible for the medicinal effects of Milk Thistle fruits: antioxidant, hepatoprotective, anticancer and chemoprotective activities. Natural silybin exists as an equimolar mixture of diastereomers A and B whose preparative separation is very hard. It was shown that the biological activity of silybin A and B are different. Silybin in the blood conjugates mainly to sulfates. The structure or biological activity of the sulfates is not yet known. The aim of this work is to develop practically applicable method for preparative separation of diastereomers of silybin A and B, and sulfates, which are considered as one of the major metabolites of silybin. The preparative method for separation of silybin A and B in the mobile phase consisting of 50% MeOH on the chromatographic column Labio C18 25x250 mm, was developed. In addition, preparative method for separation of mixture of products accured from the sulphation of silybin-23-acetate in the mobile phase consisting of MeOH/H2O 60/40 (v/v) with addition of 10 ml/l HCOOH, was optimized.
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Milk thistle (Silybum marianum) utilization in animal feeding
Klímová, Stefanie ; Lukešová, Daniela (advisor) ; Fernández Cusimamani, Eloy (referee)
Milk thistle (Silybum marianum (L.) Gaertn.) is a medicinal herb known for its hepatoprotective and antioxidant properties which not only have positive results in human medicine but also in veterinary medicine. Active substances of milk thistle are called silymarin complex and they are obtained by pressing the seeds of the plant. The bachelor thesis has a literature review of summarized findings of the use of substances contained from milk thistle in human medicine and further in animal nutrition. In the next section were selected case studies dealing with the influence of the addition of milk thistle to complete feed mixtures in laboratory animals. Milk thistle in experimental works was administered to rabbits as an antioxidant AV3 (0.2 ml.kg-1) and was followed by evaluation of metabolic parameters in comparison with the control group that was fed complete feed mixture without the addition of milk thistle. The investigated parameters were growth, biochemical and reproductive parameters and quality of rabbit meat. Addition of milk thistle did not affect the growth parameters, the quality of the flesh and blood biochemistry, compared to the control groups of animals, with the exception of the level of cholesterol, which increased by 38.6%. Reproduction parameters of milk thistle supplement increased the number of born and weaned kids and decreased offspring mortality compared to the control group. Milk thistle can therefore be used as a dietary supplement for improving reproductive parameters. Use of substance contents of milk thistle in human medicine has been evaluated in the survey from where 55 % of the 120 respondents use silymarin in tablets in the acute or chronic liver diseases for its hepatoprotective effect.
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Analysis of some biologicaly active components in natural plant extracts
Kováčová, Ivana ; Márová, Ivana (referee) ; Němcová, Andrea (advisor)
This thesis is focused on the study of the effectiveness of active ingredients from natural extracts such as milk thistle and turmeric. The thesis describes the use of modern methods of analysis and identification of active substances located in plants of milk thistle and turmeric. In the experimental part of thesis, which was preceded by a literature search focused on the biological effects of active substances in the chosen natural extracts, the extracts were characterized according to group characteristics (total assessment of polyphenols and flavonoids, assessment of antioxidant activity, and assessment of vitamin C volume and tocopherol). The next part is focused on the study of the encapsulation of natural active substances into the organic particles: liposomes. Silymarin and curcumin were encapsulated as active substances. The idea of a plant with a single active ingredient is usually erroneous. Plants usually contain hundreds of components which cooperate on a given effect. Therefore, the majority of herbalists believe that a simple plant is an active ingredient. However, some plants are known to be containing a particular active phytochemical. For instance, plants such as the milk thistle, turmeric, or a ginkgo are great examples of the plant containing a particular active phytochemical. In these cases, the active compound is disproportionately more effective than the plant itself. Encapsulation efficiency of active ingredients of Silymarin and curcumin was determined by HPLC/PDA. The aim of the analysis was to observe the behavior of elements during the incubation in surrounding of gastric juice model, and the stability while maintaining the particles in model food.
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Growing technology of milk thistle (Silybum marianum L. Gaertn.) and fertilization with the aim of maximizing the quality of the product and its use
GUBIŠOVÁ, Jana
Milk thistle (Silybum marianum L. Gaertn.) a medicinal plant known for thousands years. In the Czech Republic is purposely planted since the 70s of last century. Last few years increased worldwide interest about this plant mainly due to the pharmaceutical industry, which uses isolated of the active ingredients. The advantage of this plant is low demands on environment and high yields if suitable agrotechnics aspects and soil quality are provided. The main objective of this thesis was to gather available information about milk thistle, growing technology, and familiarity with its botanical characteristics, chemical composition and active ingredients, farming techniques, use, fertilization and past management. Furthermore the study was focused on summarizing the methods for the determination of certain active substances clarification the pharmacological effects and the influence of elicitation and cultivation techniques for the active substances. In the conclusion was summarized the problem of the cultivation of milk thistle and technology designed for growing in practice and of its use. Especially as a technology of soil preparation, choosing suitable proceeding crop, seeding, fertilizing and the most demanding plant harvest. Furthermore there was given a proposal for the use of seeds of milk thistle in the food industry, where is considered as insufficient. The potential of this medicinal plant would be for example for the production of functional foods.
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Growing Milk thistle (Silybum marianum L. Gaertn.) The content of biologically active substances and their use
HOFÍREK, Pavel
Milk thistle [(Silybum marianum) L. Gaertn] is among the longest known medical plants, described already in the 4th century before Christ. In the first part of my thesis, I studied the technology of cultivation this medical plant. Milk thistle contains biologically active substances. The main active substances are silybin, silydianin, isosilybin, silychristin, known as silymarin complex, and taxifolin. These substances have hepatoprotective effects on liver tissue. Characteristics, some methods of determination of active substances and pharmacological effect I deal with in the second part of my thesis. The content of active substances are influenced by growing technologies and applications elicitors. This issue and current use of plants in human medicine, dietary supplements and feed to attend in the end.
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Electrochemistry of Flavonolignans and their Interactions with DNA and Proteins
Pyszková, M. ; Zatloukalová, M. ; Biedermann, David ; Křen, Vladimír ; Ulrichová, J. ; Ramešová, Šárka ; Sokolová, Romana ; Vacek, J.
Electrochemical oxidation of flavonolignans silybin, silydianin, silychristin and their 2,3-dehydroderivatives, was studied using ex situ and in situ cyclic and square wave voltammetry at pyrolytic graphite electrode. The pilot results presented here could be used for further investigation of mechanism of oxidation and reactivity of flavonolignans to DNA and proteins.
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