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Modulatory effects of quercetin and rutin on cytochrome P4501A expression and activity in intestinal cells
Volková, Marie ; Skálová, Lenka (advisor) ; Trejtnar, František (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Marie Volková Supervisor: Doc. RNDr. Lenka Skálová, Ph.D. Title of diploma thesis: Modulatory effects of Quercetin and Rutin on the activity and expression of cytochrome P4501A in the intestinal cells Flavonoids originate as the secondary metabolites of plants and they are daily consumed in fruits and vegetables. They show the antioxidant, antiinflammatory, anticarcinogenic and other healthy effects. A potential anticarcinogenic effect is mediated by the strong antioxidant activity, but it can also include an inhibition of xenobiotica - metabolizing enzymes to the carcinogenic compounds. This work has examined the potential inhibition effect of the flavonoids Rutin and Quercetin on an activity and expression of cytochrome P4501A (CYP1A) in the intestinal cells. Quercetin is the most abundant flavonoid and Rutin is its most abundant glycosidic form. CYP1A is responsible for an activation of many pre - carcinogenic ingested substances. The study was conducted on the intestinal cell line HCT-8. CYP1A's enzymatic activity was measured by EROD/MROD activity; quantity of CYP1A's protein was set by Western blotting. Quercetin at the concentration of 1 µM caused slightly increased EROD/MROD...
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Interaction of Organophosphorus Poisoning Antidotes with Muscarinic and Nitotinic Receptors
Soukup, Ondřej ; Fusek, Josef (advisor) ; Trejtnar, František (referee) ; Anzenbacher, Pavel (referee)
1 Summary in English Currently, organophosphorus (OP) poisoning is a threat particularly in war conflicts in connection with terrorism or a poisoning caused by OP pesticides in agriculture. The poisoning is caused by inhibition of the enzyme acetylcholinesterase (AChE), which, under physiological conditions, cleaves acetylcholine (ACh) and regulates the transmission of nerve signals. The inhibition of AChE leads to excessive stimulation of cholinergic receptors and clinically it manifests as so-called cholinergic syndrome. According to the structures affected, symptoms are divided into nicotinic, muscarinic and central. Organophosphates are lethal compounds, when death is caused by suffocation. Current treatment is mainly based on the application of anticholinergics (atropine) and /or on the application of AChE oxime reactivators (HI-6, obidoxime, pralidoxime etc.) Atropine inhibits excessive neural transmission by blocking muscarinic receptors. However, it is only symptomatic cure not causal. Whereas oximes, which represent a causal therapy, are able to unbind an OP compound from the AChE and restore its splitting function. Using reactivators has two major drawbacks; there is no universal reactivator against all types of OP compounds (soman, sarin, paraoxon etc.) and reactivation is possible only within a...
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Mechanism of the vasorelaxant effect of biochanin A studied ex vivovon isolated rat aorta
Katiová, Diana ; Pourová, Jana (advisor) ; Trejtnar, František (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxikology Consultant: PharmDr. Jana Pourová, Ph.D. Consultant specialist: Mgr. Thomas Migkos Student: Diana Katiová Title of Thesis: Mechanism of the vasorelaxant effect of biochanin A studied ex vivo on isolated rat aorta Flavonoids are secondary plant metabolities which are known for thein wide range of effects. Many of them have beneficial effects on the human organism. Thay have anti-inflammatory properties, antioxidant activity and positive effect on cardiovascular system. The main aim of this thesis was to determine possible vasorelaxant mechanisms of action of selected isoflavonoid biochanin A. The vasorelaxation potential was verified in ex vivo conditions on isolated rat aortic rings. The results has confirmed dose-dependent induced vasodilatation. Our experiments confirm that the vasodilatatory effect of biochanin A is independent on the function of endotel. Beside that the experimental part of this thesis is dealing with the effect of this substance on Ca2+ channels of L-type in the plasma membrane and whether vasorelaxant effect is dependent on extracelullar Ca2+ . Our results confirm that similarly as nifedipine biochanin A blocks these channels as well. Moreover biochanin A in the medium without...
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Study of transport mediated by drug transporters in model cell systems
Znamínková, Jana ; Smutná, Lucie (advisor) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Jana Znamínková Supervisor: PharmDr. Lucie Hyršová, PhD. Title of diploma thesis: Study of transport mediated by drug transporters in model cell systems Liver is the main biotransformation organ of human organism. Not every substance can cross the cell membrane of hepatocytes by simple diffusion. Transport of such substances across the membrane is mediated by specialized transport proteins. Uptake transporters localized on the basolateral membrane of hepatocytes play a crucial role in uptake of compounds from blood into hepatocytes, where the biotransformation takes place. OCT1 transporter belongs between important members of this group, it transports organic cations. Efflux transporters localized on the apical membrane are responsible for transport of substances from hepatocytes to bile canalicular and these transporters mediate their elimination in this way. BCRP is an example of this group of transporters. Drug transporters represent one of the most important mechanisms of drug-drug interactions due to their wide range of substrates. The aim of this study was to evaluate the function of novel cell models using substrate and inhibitors of these transporters. Stably transfected MDCK II cells...
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Potential toxicity of terpenes and their effects in liver cells
Zárybnický, Tomáš ; Boušová, Iva (advisor) ; Anzenbacherová, Eva (referee) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Tomáš Zárybnický Supervisor: assoc. prof. PharmDr. Iva Boušová, Ph.D. Consultant: assoc. prof. Ing. Petra Matoušková, Ph.D. Title of Doctoral Thesis: Potential toxicity of terpenes and their effects in liver cells The public interest in herbal products, supplements, extracts or isolated active compounds has been increasing during last decades. The aim of this doctoral thesis was to study selected compounds from the group of monoterpenes and sesquiterpenes and their interactions with liver cells: interactions with drug metabolising enzymes, their potential liver toxicity and looking for novel mechanisms of action. The literature about hepatotoxic properties of several monoterpenes and sesquiterpenes, that showed liver toxicity, was summarized first. Then, the study was aimed toward a known hepatotoxicant (R)-pulegone and its presumed metabolite (R)- menthofuran. The toxicity results in precision-cut human liver slices have shown that (R)- menthofuran was less toxic to human liver and that the reason may be inter-species differences between human and mice. Several sesquiterpenes (farnesol, cis-nerolidol, trans-nerolidol, α-humulene, β-caryophyllene, and caryophyllene oxide) have previously...
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Recent knowledge on drug effect on male fertility
Klapková, Tereza ; Trejtnar, František (advisor) ; Hyršová, Lucie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Tereza Klapková Supervisor: Assoc. Prof. PharmDr. František Trejtnar, CSc. Title of diploma thesis: Recent knowledge on drug effect on male fertility Among the various types of side effects presented in clinically used drugs, negative effects on male reproductive functions can be find. This issue seems to be important and current especially due to the general trend of the decrease in fertility in men and the increasing drug use in younger age groups. The aim of this diploma thesis was to create an overview summarizing current expert knowledge on the effect of drugs on male fertility. For this purpose, we selected relevant publications in the PubMed database, perform their analysis and create the text ofthe thesis. The review focuses mainly on groups of drugs that are often clinically used and discussed in relation to male fertility, such as drugs acting on the cardiovascular system, antimicrobial drugs, drugs used in pain therapy, antidepressants, antiepileptics, antipsychotics, immunosuppressants and some other drugs. In addition to standard drugs, the review also includes several important natural substances, which are used as adjunctive therapy of various diseases or are important from a...
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Study of transport mediated by drug transporters in model cell systems
Znamínková, Jana ; Hyršová, Lucie (advisor) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Jana Znamínková Supervisor: PharmDr. Lucie Hyršová, PhD. Title of diploma thesis: Study of transport mediated by drug transporters in model cell systems Liver is the main biotransformation organ of human organism. Not every substance can cross the cell membrane of hepatocytes by simple diffusion. Transport of such substances across the membrane is mediated by specialized transport proteins. Uptake transporters localized on the basolateral membrane of hepatocytes play a crucial role in uptake of compounds from blood into hepatocytes, where the biotransformation takes place. OCT1 transporter belongs between important members of this group, it transports organic cations. Efflux transporters localized on the apical membrane are responsible for transport of substances from hepatocytes to bile canalicular and these transporters mediate their elimination in this way. BCRP is an example of this group of transporters. Drug transporters represent one of the most important mechanisms of drug-drug interactions due to their wide range of substrates. The aim of this study was to evaluate the function of novel cell models using substrate and inhibitors of these transporters. Stably transfected MDCK II cells...
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Changes in expression of biotransformation enzymes in nematodes affected by albendazole
Štěrbová, Karolína ; Skálová, Lenka (advisor) ; Trejtnar, František (referee)
5 ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Bc. Karolína Štěrbová Supervisor: prof. RNDr. Lenka Skálová Ph.D. Title of diploma thesis: Changes in expression of biotransformation enzymes in nematodes affected by albendazole Barber's pole worm (Haemonchus contortus) is highly pathogenic parasitic nematode, which assaults gastrointestinal system of small ruminants. Disease. Which caused is named by the agent haemonchoses. Long-term infection leads to develop of anaemia, lose weight of host and often even death. For treatment of this disease, synthetic antiparasitic drugs called anthelmintics are used. However, worldwide problem is growth of resistance against all used anthelmintics. Cause of this problem is probably common and unreasonable using of anthelmintics and the exposure of the parasites to sub-lethal doses. This thesis is focused on study of the mechanisms of resistance of barber's pole worm to albendazole, anthelmintic belonging to benzimidazoles group. The increased expression of biotransformation enzymes could contribute to resistance development. In our study, the influence of albendazole on expression of selected genes in adults of H. contortus from the ISE (Inbread Susceptible Edinburgh) strain was studied. Worms...
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Analysis of drug problems at hospital department from the pharmacist's point of view
Dvořáčková, Eliška ; Vlček, Jiří (advisor) ; Trejtnar, František (referee) ; Urbánek, Karel (referee)
práce v anglickém jazyce Title: Analysis of drug problems at hospital department from the pharmacist's point of view Introduction: Chronic kidney disease is a medical and economic problem. It affects 10-13 % of the population in European countries and incidence is increasing with every decade of life. The most common cause of kidney failure in patients over 50 years of age is associated with 2. type diabetes and hypertension. Chronic kidney disease is associated with risk of mortality, hospitalization and decreased quality of life. Clinical pharmacist as a specialist in a field of pharmacotherapy collaborates with other health professionals to optimize pharmacotherapy. Proactive approach with active prevention of drug related problems (DRPs) is preferre. Identification and minimization of drug problems together with optimization of pharmacotherapy are the main objectives of clinical pharmacy. Where the prerequisite for the detection and resolution of drug problems is not only knowledge of pharmacology but also other medical disciplines such as biochemistry, microbiology, pathophysiology and epidemiology. This work is one of the first publications of this type in the Czech Republic, which reveals a review of pharmacotherapy in patients with chronic kidney disease and the integration of a pharmacist...
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The study of properties of radiolabelled monoclonal antibodies for imaging in oncology
Janoušek, Jiří ; Trejtnar, František (advisor) ; Kozempel, Ján (referee) ; Lázníčková, Alice (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Jiří Janoušek, MSc. Supervisor: Assoc. Prof. PharmDr. František Trejtnar, CSc. Consultant: Mgr. Pavel Bárta, Ph.D. Title of doctoral thesis: The study of properties of radiolabelled monoclonal antibodies for imaging in oncology Monoclonal antibodies belong to the group of targeted biological drugs that are currently successfully applied in various medical specialties, including oncology. The ability to specifically bind to antigens present in a tumour tissue is their significant attribute that can be used for imaging tumours in Nuclear Medicine. Receptors for vascular endothelial growth factor (VEGFR) and epidermal growth factor (EGFR) are possible tumour specific targets that are characteristic for some types of proliferating tumour tissue. The attachment of appropriate radionuclide is necessary for the potential radiodiagnostic use of monoclonal antibody. This task requires chemical modification of the antibody molecule that can damage its immunoreactivity and the binding to the target receptor. The aim of the doctoral thesis was to study the influence of labelling conditions with selected diagnostic radionuclides on radiochemical characteristics, in vitro receptor specific binding and...
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