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The role of drug transporters in activation of pregnane X receptor
Kejvalová, Kateřina ; Smutná, Lucie (advisor) ; Pourová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kateřina Kejvalová Supervisor: PharmDr. Lucie Smutná, Ph.D. Title of diploma thesis: The role of drug transporters in activation of pregnane X receptor The nuclear pregnane X receptor (PXR) is involved in maintaining the homeostasis of endogenous substances as well as in regulation of excretion of exogenous substances. PXR activation regulates the expression of transport and biotransformation enzymes I. and II. phase. Due to the high flexibility of PXR ligand binding domain, it can be activated by a wide range of xenobiotics. Including e.g., rifampicin, well-known PXR agonist causes clinically significant drug-drug interactions. However, rifampicin is not stable under physiological conditions and degradation occurs (into rifampicin quinone, 25-desacetylrifampicin, 3-formylrifamycin SV and rifampicin N-oxide). The aim of our experiments was to compare the interspecies activation of PXR (human, monkey, mouse and rat) by rifampicin and its derivatives. Hence, gene reporter experiments were performed using the HepG2 cell line. Statistically significant results in PXR activation were observed for human hPXR and monkey oPXR for all rifampicin derivatives except 25- desacetylrifampicin. Similarity...
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Vasodilatory effects of 4-methyl catechol: ex vivo mechanism of action
Kuzdřalová, Kateřina ; Pourová, Jana (advisor) ; Smutná, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kateřina Kuzdřalová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: The mechanism of vasodilation effect of 4-methylcatechol ex vivo Keywords: rat, aorta, flavonoids, 4-methylcatechol, vascular smooth muscle, vasodilation Flavonoids belong to the group of polyphenolic bioactive substances found abundantly in plants, fruits and vegetables. Thanks to their pharmacological and biochemical effects, they play a crucial role for human health, especially in the prevention of numerous diseases - metabolic syndrome, osteoporosis, atherosclerosis and also diseases of a cardiovascular system. The aim of the diploma thesis was to determine the mechanism of the vasorelaxant effect of one of the most important metabolites of flavonoids - 4-methylcatechol. For the research we used a standardized ex vivo method on isolated Wistar rat aortic rings. We were able to confirm the vasodilatory effects of 4-methylcatechol. We also confirmed the fact that the flavonoid metabolite directly affects a vascular smooth muscle. Furthermore, we found that the tested compound potentiates the vasodilatory activity of sodium nitroprusside and forskolin, and that vasodilation depends on the activity of...
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Current therapeutic options for the traetment of anorexia and bulimia
Kašová, Kristína ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
1. Abstract Author: Title: Form: Name of University: Degree: Department of: Consultant: Kristína Kašová Current therapeutic options for the treatment of anorexia and bulimia Diploma Thesis Charles University in Prague, Faculty of Pharmacy in Hradec Králové Pharmacy Pharmacology and Toxicology PharmDr. Jana Pourová, Ph.D. The work deals with therapy of mental anorexia and bulimia and targets to collect the information about opportunities for pharmacotherapy of these diseases which can be provided as a supportive treatment together with psychotherapeutic-psychological methods. In recent years the incidence of eating disorders has rapidly increased and there are several reasons for this growth. We focus not only on the current therapeutic options for the treatment of these diseases but we also try to point out the danger which goes hand in hand with eating disorders, health complications and raising mortality of patients with the diagnosis of mental bulimia and mental anorexia. Key words: mental anorexia, mental bulimia, psychotherapeutical methods, pharmacotherapy
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Vasodilatory effects of 3-hydroxy phenylacetic acid: ex vivo mechanism of action
Štefancová, Monika ; Pourová, Jana (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Monika Štefancová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Vasodilatory effects of 3-hydroxy phenylacetic acid: ex vivo mechanism of action It is known from clinical studies that the intake of polyphenols from food acts as a prevention of cardiovascular diseases. However, the parent compounds themselves often have low bioavailability. The emphasis is therefore on their bioactive metabolites. 3-hydroxy phenylacetic acid (3-HPAA) is among such metabolites. The aim of this study was to verify the mechanism of the vasodilatory effect of 3-HPAA using standardized ex vivo method on an isolated pig coronary artery. The administration of 3-HPAA resulted in relaxation of maximally contracted segments of porcine artery by mechanism partially dependent on the integrity of endothelium. By inhibiting endothelial nitric oxide synthase, the relaxation was significantly impaired. The blockage of SKCa and IKCa channels, muscarinic receptors, cyclooxygenase or L-type calcium channels did not affect relaxation. Thus, 3-HPPA causes dose-dependent vasodilatation of coronary arteries ex vivo at least partially mediated by endothelium with the participation of nitric oxide. Key words:...
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Vasodilatory effects of 4-methyl catechol: ex vivo mechanism of action
Kuzdřalová, Kateřina ; Pourová, Jana (advisor) ; Smutná, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kateřina Kuzdřalová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: The mechanism of vasodilation effect of 4-methylcatechol ex vivo Keywords: rat, aorta, flavonoids, 4-methylcatechol, vascular smooth muscle, vasodilation Flavonoids belong to the group of polyphenolic bioactive substances found abundantly in plants, fruits and vegetables. Thanks to their pharmacological and biochemical effects, they play a crucial role for human health, especially in the prevention of numerous diseases - metabolic syndrome, osteoporosis, atherosclerosis and also diseases of a cardiovascular system. The aim of the diploma thesis was to determine the mechanism of the vasorelaxant effect of one of the most important metabolites of flavonoids - 4-methylcatechol. For the research we used a standardized ex vivo method on isolated Wistar rat aortic rings. We were able to confirm the vasodilatory effects of 4-methylcatechol. We also confirmed the fact that the flavonoid metabolite directly affects a vascular smooth muscle. Furthermore, we found that the tested compound potentiates the vasodilatory activity of sodium nitroprusside and forskolin, and that vasodilation depends on the activity of...
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The role of drug transporters in activation of pregnane X receptor
Kejvalová, Kateřina ; Smutná, Lucie (advisor) ; Pourová, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Kateřina Kejvalová Supervisor: PharmDr. Lucie Smutná, Ph.D. Title of diploma thesis: The role of drug transporters in activation of pregnane X receptor The nuclear pregnane X receptor (PXR) is involved in maintaining the homeostasis of endogenous substances as well as in regulation of excretion of exogenous substances. PXR activation regulates the expression of transport and biotransformation enzymes I. and II. phase. Due to the high flexibility of PXR ligand binding domain, it can be activated by a wide range of xenobiotics. Including e.g., rifampicin, well-known PXR agonist causes clinically significant drug-drug interactions. However, rifampicin is not stable under physiological conditions and degradation occurs (into rifampicin quinone, 25-desacetylrifampicin, 3-formylrifamycin SV and rifampicin N-oxide). The aim of our experiments was to compare the interspecies activation of PXR (human, monkey, mouse and rat) by rifampicin and its derivatives. Hence, gene reporter experiments were performed using the HepG2 cell line. Statistically significant results in PXR activation were observed for human hPXR and monkey oPXR for all rifampicin derivatives except 25- desacetylrifampicin. Similarity...
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Vasodilatory effects of catechol derivatives ex vivo
Šmídová, Kristýna ; Pourová, Jana (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Kristýna Šmídová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Vasodilatory effects of catechol derivatives ex vivo Polyphenols, including flavonoids, are a broad group of natural substances with significant effects on human health, including the prevention of cardiovascular diseases. Their metabolites can also be active, with clinical effects which may even exceed those of the parent compounds. The aim of this diploma thesis was to verify vasodilatory effects of one flavonoid metabolite type, a series of catechol derivatives and elucidate the mechanism of action of the most potent substance. The established ex vivo method of isolated aortic rings of Wistar rats with isotonic registration of tissue contraction and dilation (software S.P.E.L. Advanced Kymograph Software) was used. In the experiments with the rat aorta precontracted by norepinephrin, 3-methoxycatechol was the most effective vasodilator (EC50 = 7,6 µmol.l-1). In the mechanistic study, we found out that its effect is endothelium-independent, and that 3-methoxycatechol enhances the vasodilatory effect of sodium nitropruside. However, the specific mechanism responsible for vasodilation was not identified and...
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Vasodilatory effects of catechol derivatives ex vivo
Šmídová, Kristýna ; Pourová, Jana (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Kristýna Šmídová Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Vasodilatory effects of catechol derivatives ex vivo Polyphenols, including flavonoids, are a broad group of natural substances with significant effects on human health, including the prevention of cardiovascular diseases. Their metabolites can also be active, with clinical effects which may even exceed those of the parent compounds. The aim of this diploma thesis was to verify vasodilatory effects of one flavonoid metabolite type, a series of catechol derivatives and elucidate the mechanism of action of the most potent substance. The established ex vivo method of isolated aortic rings of Wistar rats with isotonic registration of tissue contraction and dilation (software S.P.E.L. Advanced Kymograph Software) was used. In the experiments with the rat aorta precontracted by norepinephrin, 3-methoxycatechol was the most effective vasodilator (EC50 = 7,6 µmol.l-1). In the mechanistic study, we found out that its effect is endothelium-independent, and that 3-methoxycatechol enhances the vasodilatory effect of sodium nitropruside. However, the specific mechanism responsible for vasodilation was not identified and...
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Drugs used in clinical practice with the origin in plants
Šímová, Markéta ; Suchánková, Daniela (advisor) ; Pourová, Jana (referee)
Charles Univerzity, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmacognosy and Pharmaceutical botany Author: Markéta Šímová Supervisor: PharmDr. Daniela Hulcová Ph.D. Title of thesis: Active substances used in clinical practice originating in plant sources Key words: active substance, plant source, development, analgesics, local anesthetics, antineoplastics, sympathomimetics, parasympathomimetics, parasympatholytics, antispasmodics. Since time immemorial, plants have been used to treat various diseases, but it is not known what is behind their healing effect. It managed to find out with the development of pharmacy and chemistry. The first substances were isolated and their mechanism of action was elucidated. It was found that the substances themselves have a better and more efficient effect than the mixture, but also a number of side effects. The effort of experts was to remove them, which managed to prepare a lot of derivatives and in many cases they had even higher effect. With the development of new technologies, synthetically produced substances have come to the fore and it is already forgotten that many clinically used drugs have their origins in nature. This thesis deals with substances that originate in plant sources and are used in clinical practice as medicinal...
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Natural drugs in the treatment of productive cough
Čontofalská, Natália ; Pourová, Jana (advisor) ; Karlíčková, Jana (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Natália Čontofalská Supervisor: doc. PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Natural drugs in the treatment of productive cough Cough is a physiological defensive reflex and it is also a symptom of many acute or chronic diseases. Cough can be categorized as dry irritant or productive. Productive cough can be treated by conventional drugs and medicinal plants. Medicinal plants contain various types of chemicals and some of them have expectorant properties. Chemical constituents are commonly members of saponin, flavonoid or essential oil groups. This diploma thesis presents summary of the most important results and information from literature, pharmacological experiments and clinical studies confirming their efficiancy. Some of the articles provide explanation of mechanism of action of the chemicals with expectorant properties. Other effects of these plants may also contribute to the therapeutic effect.
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