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Troxerutin and its therapeutic use
Zuranová, Jana ; Mladěnka, Přemysl (advisor) ; Pávek, Petr (referee)
This diploma thesis is aimed at description characteristics and use of troxerutin in the clinical and the experimental practice. The first part of this thesis describes flavonoids as original substance. It includes theirs classification, chemical structure, common and potentionally beneficial pharmacodynamics properties. The main part of this thesis characterizes troxerutin. Troxerutin is a semisynthetic derivate of rutin. Its pharmacodynamics activities has been used therapeutically in the treatment of chronic venous insufficiency for more 30 years. Its positive is based on its antithrombotic, fibrinolytic, odemaprotective, blood viscosity and leukocyte endothelium-wall adherence decresing properties. Troxerutin directly affects erythrocytic aggregation particullary marked at high doses and it facilitation higher afflux of blood to the microcirculation. Its antioxidative effect is important too. The main indications of troxerutin at the present are chronic venous insufficiency and hemorrhoids. Simultaneously is experimentaly examined in a range of disorder, for example in the therapy of common cold, diabetic retinopathy and lymphoedema. In the Czech republic, troxerutin is available perorally in the form (Cilkanol® , Ginkor fort® and Venoruton® ) and locally as gel in Venoruton® gel.
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The effect of polyphenolic substances on vascular smooth muscle
Najmanová, Iveta ; Mladěnka, Přemysl (advisor) ; Tůmová, Lenka (referee) ; Klimas, Ján (referee)
[Sem zadejte text.] Abstract Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Iveta Najmanová, MCs First Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Second Supervisor: Marie Vopršalová, Pharm.D., Ph.D. Title of Doctoral Thesis: The effect of polyphenolic substances on vascular smooth muscle Polyphenolic substances are one of the most abundant secondary plant metabolites. Many substances from simple phenols with one benzene core to the polymeric compounds belong to these groups. Two groups, coumarins and flavonoids, were selected for this dissertation. The aim of this thesis was to analyse their effect on vascular smooth muscle in in vitro and in vivo conditions. In the case of coumarins, the aim was reached by writing of a review article. The effect of flavonoids, including their metabolites was experimentaly tested and some of the results have already been published. The first step in my research was to perform a screening of metabolites of quercetin, the most occuring flavonol in the human diet, and compare their vasorelaxant potential. Experiments were performed on isolated rat thoracic aorta. During the testing, the most effective metabolite was definitely 3-(3-hydroxyphenyl)propionic acid (3-HPPA), which was at least one order...
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Effect of lactoferrin on macroscopical and histological features in different tissues in rats. II. Liver and kidneys.
Škrle, Jan ; Semecký, Vladimír (advisor) ; Mladěnka, Přemysl (referee)
Lactoferin is an 80-kDa iron-binding glykoprotein. It shares a high degree of homology at amino acid sequence level and also the three dimensional conformation level with transferin. Both proteins are classified in the family of iron-binding glykoproteins, named transferin family. Afinity of Lf to iron is about 260times higher than that of transferin. (1) Lf is present physiologically in exocrine secretions, eg. tears, saliva, milk, sinovial fluid, seminal fluid and in the secondary granules of neutophils. (6) The precise function of Lf in organism is considered to be very complex and is still a hot subject of scientific disputation. Lf was documented to act as antimicrobial, antiinflamatory and antitumoral agent. (15,17) Another of its properties is ability to inhibit hydroxyl radical formation via Fenton reaction. (20) Because of good technological properties and it's physiological occurence Lf can be used as a therapeutical agent.(6) In our experiment we studied the influence of Lf on macroscopical and histological features in liver and kidney of the sewer-rat. We used two-dose model of i.v. Lf ( 50mg/kg in one dose and 3x 20 mg/kg in three days). The tissues of both models were used for histopatological analysis. We observed significant patological changes in kidney and liver after i.v....
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Comparsion of iron reducing properties of flavonols and flavanones
Kyjovská, Veronika ; Mladěnka, Přemysl (advisor) ; Karlíčková, Jana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Veronika Kyjovská Supervisor: P emysl Mlad nka, Ph.D. Title of Thesis: Compare iron-reducing properties of flavanols and flavanons The aim of this thesis was to compare the iron-reducing properties of flavanons and flavonols in different concentrations, at different pathophysiological pHs and in non-buffered conditions. A spectrophotometric method with ferrozin, an indicator of ferrous ions, was used. Results at pH 4.5 and in non-buffered conditions were almost comparable, while at pH 5.5 flavonoids showed almost no reduction activity. At pH 6.8 and 7.5 flavonoids did not reduce ferric ions at all. Representatives with the highest reduction activity belonged mostly to the group of flavonols (quercetin, kaempferol, morin, myricetin). Only one representative of flavanons - taxifolin showed the same reduction activity as aforementioned representatives of flavonols. This is probably due to the presence of the 3-hydroxy group in C ring. Other representatives of flavonon do not contain this group and were associated with minimal capabilities of reduction. Lower reduction activity was also observed in case of a representantive of flavonols - rutin, which has the 3-hydroxy group substituted...
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The pharmacokinetics of isoflavonoides
Ungerová, Lucie ; Pourová, Jana (advisor) ; Mladěnka, Přemysl (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucie Ungerová Supervisor: PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: The pharmakokinetics of isoflavonoids The aim of this diploma thesis is to summarize currently available informations about the pharmacokinetics of the polyfenolic compounds from a large group of flavonoids, isoflavonoids. Isoflavonoids are coumpounds found in many plant families, but especially in some members of Fabaceae family. One of the main well-known sources are soy beans containing the most famous isoflavones - genistein and daidzein, their pharmakokinetics is the main theme of this diploma thesis. Since isoflavonoids are mainly contained in the diet, their oral administration is very relevant. Isoflanonoids in the human diet occurs predominantly in the form of glykosides and therefore, after ingestion, they have to be deglycosylated by β- glucosidase enzyme family to aglycones. After that they are able to pass through the intestine into the systemic circulation and they are available for action. This is already happening in the oral cavity and the absorption occurs in the small intestine. The intestinal bacterial microflora composition is also very important for pharmacokinetics, for example I can mention...
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Effect of Nicotinic Acid on infiltration of macrophages in the ischemic brain
Pokorná, Barbora ; Pávek, Petr (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Kralove Department of Pharmacology and Toxicology Candidate: Barbora Pokorna Supervisor: Doc. PharmDr. Petr Pavek Ph.D. Specialized supervisor: Prof. Dr. med. Markus Schwaninger Title of diploma thesis: Effect of Nicotinic Acid on infiltration of macrophages in the ischemic brain Stroke is one of the leading causes of death worldwide and its effective protective treatment is still missing. Nicotinic acid has been a widely used substance to modify lipid profiles for many years and it successfully prevents clinical cardiovascular diseases. Recently explored receptor, GPR109A, causes its effect and it was found to be expressed in spleen, adipose, and immune cells including macrophages. The aim of this work is to investigate the effect of nicotinic acid on the infarct size during cerebral ischemia and to determine the role of macrophages in its effect. We compared two groups in our experiments, transgenic CD11bDTR mice and control wild type (WT) mice. Both groups were treated with diphtheria toxin (DT), then a middle cerebral artery occlusion was performed and afterwards mice were treated with either nicotinic acid or vehicle. We have found depletion of macrophages in CD11bDTR group induced by DT treatment and depletion of macrophages in WT...
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Modulace exprese alfa-synukleinu pomocí působení 5-S-cysteinyldopaminu na buňky lidského neuroblastonu SH-SY5Y: možná úloha katecholthioetherů při neurodegeneraci
Hrabáková, Rita ; Štaud, František (advisor) ; Mladěnka, Přemysl (referee)
-Synuclein is a presynaptic protein which has been demonstrated to be involved in PD etiopathogenesis.It can regulate DA homeostasis by inhibition of TH activity, by regulation of the DAT activity and finally by potential role in vesicular storage. - Synuclein is a natively unfolded protein, which can undergo overexpression and aggregation due to toxic insults or oxidative stress. The aggregation of α-synuclein leads to a loss of function, which in PD neurons may determine a dysregulation of the DA pathways with subsequent excess of cytosolic DA, that can enhance the neurotoxic effect of α-synuclein aggregates. In recent years, a catecholthioether metabolite of DA, 5-S-cysteinyl-dopamine, has been identified in certain dopaminergic regions of the brain, notably the Substantia nigra. Cys-DA seems to have a possible significance as an index of oxidative stress in aging and in neurodegenerative processes and it was recently hypothesized that this substance or its metabolites may be the endogenous neurotoxins responsible for neurodegeneration in PD. Hence, the aim of this experimental work was to determine whether Cys-DA is able to cause overexpression of -synuclein both at transcriptional and translational levels in a cellular model of PD, the human neuroblastoma dopaminergic cell line SH-SY5Y....
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Identification and characterization of G protein-coupled nucleotide and nucleotide-like receptors P2Y13 and GPR17
Klenotič, Ondřej ; Doležal, Martin (advisor) ; Mladěnka, Přemysl (referee)
Identification and characterization of G protein-coupled nucleotide and nucleotide-like receptors P2Y13 and GPR17 Purinergic receptors are divided into three subfamilies, P1 (adenosine), P2 (nucleotide) and P0 (adenine) receptors. P2 receptors comprise ligand-gated ion channels - shortly LGICs, receptors P2X1-7, and class A, δ-branch GPCRs termed P2Y1,2,3,6,12-14. The P2Y13 receptor is physiologically activated by ADP and coupled to Gi whose activation results in an inhibition of adenylate cyclase. P2Y13 receptor activation has been reported to be neuroprotective. P2Y13 receptors also play a role in lipoprotein metabolism and cholesterol transport, making the receptor an interesting target for the potential treatment of atherosclerosis. The nucleotide-like orphan receptor GPR17, whose endogenous agonist remains still unknown, is also Gi-coupled. GPR17 appears to be involved in demyelinating diseases such as multiple sclerosis, and some inflammatory diseases. The development of potent, selective ligands, agonists and antagonists, for both P2Y13 and GPR17, is required to study their physiological and pathophysiological roles and for validating the receptors as future drug targets. In the present study, we aim to find out, if the approach via β-arrestin assay employing an enzyme complementation is...
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Copper chelating properties of flavanones
Kantorová, Tereza ; Mladěnka, Přemysl (advisor) ; Spilková, Jiřina (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Departmet of Pharmacology and Toxicology Candidate: Tereza Kantorová, MSc. Consultant: Assoc. Prof. Přemysl Mladěnka, Pharm.D.,PhD. Title of the Rigorous Thesis: Copper chelating properties of flavanones Copper is an essential trace element playing an essential role in our body. As part of couproenzymes, it is involved in many physiological processes. However, at the same time, it also poses a certain risk to the human body. Free copper has the ability to potentiate the formation of reactive oxygen species and thus to promote oxidative stress. Therefore, copper homeostasis must be carefully regulated. Flavanones belong to one of the subclasses of flavonoids. These natural substances are very interesting from a scientific point of view due to their possible various pharmacological effects. In this work, we focused on their copper-chelating properties. Flavanones, which are expect to possess a low potential for side effects, could find application as copper chelators and thus expand the current therapeutic modalities for some diseases associated with copper imbalance (e.g. Wilson's disease, tumors). Four selected flavanones (hesperetin, hesperidin, naringenin and naringin) were tested for their ability to chelate copper ions using two...
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Search of effective cobalt chelators - 8-hydroxyquinolines
Pelnářová, Karolína ; Mladěnka, Přemysl (advisor) ; Carazo Fernández, Alejandro (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Karolína Pelnářová Supervisor: Prof. Přemysl Mladěnka, PharmD., Ph.D. Consultant: Václav Tvrdý, MSc.; Marcel Hrubša, MSc. Title of diploma thesis: Searching of effective cobalt chelators - 8-hydroxyquinolines Cobalt is one of the essential trace elements present in the human body. It forms a part of the organometallic complex of vitamin B12, which is essential for many physiological functions. Both overload and lack of cobalt in the body is associated with pathological conditions. Manifestations of deficiency can lead up to pernicious anemia or hypofunction of the thyroid gland. Cobalt intoxication can occur in an industrial environment, such as by cobalt metal dust during heavy metal processing, or by its release due to corrosion from orthopedic prostheses. Systemic toxicity is manifested by a number of endocrine, cardiovascular and neurological symptoms. The main aim of this diploma thesis was to find effective chelators of cobalt from the group of substances derived from 8-hydroxyquinoline. In vitro spectrophotometric measurement was used to determine the degree of chelation. The effect of chelation was also monitored ex vivo in rat erythrocytes. All tested chelators - 8-hydroxyquinoline,...
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