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The in vitro effects of selected substances on isolated rat aorta
Beránková, Anna ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Beránková Supervisor: PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: The in vitro effects of selected substances on isolated rat aorta Flavonoids are a numerous group of secondary plant metabolites. Flavonoid compounds are substances widely extended in nature and many of them have a positive influence on human health, primarily for their vasodilatory, antioxidant and anti- inflammatory effects. Three substances were selected for this diploma theses: two substances of isoflavonoid group, genistin and genistein, and the end product of genistein metabolism, 4-ethylphenol. The aim of this work is examination of vasorelaxant effects of this substances in vitro. Vasorelaxing potential of tested substances was tested in vitro in isolated aortic rings of Wistar rat. The effect of increasing doses of individual substances in precontracted aortic rings with intact endothelium was measured. From the obtained values of vessel tension, the DRC curves and EC50 values were created. The results were evaluated. The results analysis shows, that genistein (EC50 2,903.10-5 M) had the most significant activity. Also genistin (EC50 4,045.10-4 M) and high doses of 4-ethylphenol (EC50 1,509.10-3 M) caused...
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The role of succinic acid in cardiac ischemic tolerance in rats
Kordač, Petr ; Neckář, Jan (advisor) ; Husková, Zuzana (referee)
Succinate is one of the intermediate in the Krebs cycle, which in recent years has been shown to interfere with other cellular events, some of which may affect cardiac ischemic tolerance. The aim of this project was to clarify its cardioprotective role in rat hearts subjected to acute ischemia-reperfusion. The myocardial resistance to acute ischemia (infarct size and incidence and severity of ischemic and reperfusion arrhythmias) was analyzed using the Langendorff method of isolated perfused heart at a constant flow with acute succinate administration. Local ischemia was induced by ligation of left anterior descending coronary artery. Acute administration of 1 mM succinate before 60 minutes of ischemia or before reperfusion only had a beneficial effect on reducing the infarct size by 25-30 % compared to the control group. At the same time, it had an adverse effect on the incidence and severity of ischemic and reperfusion arrhythmias. Key words: Succinate, heart, rat, heart-attack, ventricular arrhythmias
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The effect of morphine withdrawal on the catecholaminergic and serotonergic neurotransmitter system in rat brain
Nováková, Daniela ; Novotný, Jiří (advisor) ; Drastichová, Zdeňka (referee)
The aim of this diploma thesis is to study the effect of morphine withdrawal on catecholaminergic and serotonergic neurotransmitter system in rat brain. Theoretical part of this thesis summarizes basic information known about principles of neurotransmission with focus on the catecholaminergic and serotonergic system, metabolism of its components, their signaling, relevant receptors, their distribution, and especially their effect on morphine dependence and subsequent withdrawal. It also summarizes briefly principles of opioid signaling and outlines the findings yet known about neurochemical analysis of the transmitter systems mentioned above. Experimental part of this thesis is focused on the optimization of the method of high performance liquid chromatography with fluorescence detection and its subsequent use to determine basic components of catecholaminergic and serotonergic neurotransmitter system in samples of different part of brain of rats affected by intraperitoneal administration of morphine sulphate, and its subsequent withdrawal and correspondings unaffected control rats. The expression of selected catecholaminergic receptors in identical samples is also detected. This thesis succesfully implements gradient into the originally isocratic method of high performance liquid chromatography...
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Development of the rat circadian system under constant light conditions
Petrželková, Lucie ; Bendová, Zdeňka (advisor) ; Kopřivová, Jana (referee)
The circadian system is a mechanism designed to generate circadian time and to synchronize it with the solar cycle. Its function is to adjust to behavioral and physiological function with the 24-hour period. The adjustment is performed using a so-called zeitgeber or synchronizer. The main circadian clock is in the suprachiasmatic nuclei (SCN) in the hypothalamus. Prolonged exposure of the organism to constant light conditions results in desynchronization of the circadian clock, which can lead to many pathologies. The impact of light at night on the organism has been studied for a long time, but the question of the impact of constant light on the development of the circadian system of the organism has been less studied. My thesis deals with this issue. Using RT-qPCR I investigated how the rhytm changes in the expression of selected clock genes in selected parts of the rat's brain, which has been kept in constant light sice birth. I also tested the impact of exposure to constant light on the early development of rhytm in locomotor activity later in the rat's life. Keywords: circadian system, photic entrainment, desynchronization under constant light, development, rat
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Vasodilatory effects of bisphenol AF ex vivo
Kuchařová, Nela ; Pourová, Jana (advisor) ; Vopršalová, Marie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Nela Kuchařová Supervisor: PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: Vasodilatory effects of bisphenol AF ex vivo Bisphenols are organic compounds used in the manufacture of plastics, resins, varnishes and lot of other products. However, their effects on human body are associated with a number of adverse effect that need to be investigated in more detail. The aim of this diploma thesis was to determine whether bisphenol AF has vasodilating effects ex vivo and to verify the mechanism of the relaxing effect. The experiments were performed on an isolated thoracic aorta of a Wistar rat. Bisphenol AF was added cumulatively to the precontracted aorta at increasing concentrations and we monitored whether vasodilation was induced. In testing the mechanism of action, we used inhibitors of the mechanisms tested during the experiment. The obtained results were evaluated using the GraphPad Prism program. The results show that bisphenol AF has a dose-dependent ex vivo vasodilatory effect (EC50 = 57.16 μmol/l). The mechanism of this effect is the blockage of voltagegated calcium channels on the vascular smooth muscle cell. The participation of other tested mechanisms has not been confirmed. Key...
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The role of cold acclimation in activation of adrenegic and thyrode signalling pathway in rat myocardium
Tibenská, Veronika ; Žurmanová, Jitka (advisor) ; Babula, Petr (referee) ; Tribulová, Narcisa (referee)
Despite advances in research and therapy, cardiovascular diseases are still the leading cause of death worldwide. A closer understanding of the endogenous protective mechanism may improve pharmacological interventions for the treatment of heart diseases. Cold acclimation or hardening has strong potential for reducing cardiovascular risk and the literature shows that it stimulates the β-adrenergic and thyroid systems in tissues. At the same time, the adrenergic system in the heart is one of the main regulators of cardiac activity. However, these signaling pathways have surprisingly not been studied at the protein level in the heart yet, and no studies can be found on the subject matter in current literature. Our results show a reduced infarct size induced by ischemic injury in cold-acclimated rats (CA) at 8 ř C for 5 weeks and then returning to normothermic conditions for 2 weeks (CAR). The aim of this dissertation is to determine, the degree of involvement of the adrenergic system in the myocardium during acclimation after 3 days, 10 days, 5 weeks of CA and subsequent CAR at the level of all three β-adrenergic receptor isoforms (β-ARs) and their signaling pathways. The results show unchanged signaling of β1-AR-Gs-adenylyl cyclase-protein kinase A in the cardioprotective regimes CA and CAR, whose...
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Expression of enzymes of kynurenine and methoxyindole pathway in the rat pineal gland, liver and heart in circadian profile and after lipopolysacharide administration
Hrubcová, Leona ; Bendová, Zdeňka (advisor) ; Svobodová, Irena (referee)
Tryptophanis anaminoacidwhichhasmanyfunctionsinthebody. Besidesitsparticipationin theproductionofproteins,itactsasasubstrateforthekynurenineandmethoxyindolemetabolic pathways. The kynurenine pathway ends with the production of nikotinamid e adenin dinukleotide ( NAD + ) ,whichisneededfortheproductionofcellularenergy. Thus,withincreased energy demand during immune system activation, the activity of the kynurenine pathway is increased. Dueto increasedactivity,itproduces more immunoactiveandneuroactivemetab olites suchaskynurenicacidandquinolinicacid.Thesemetabolitesareinvolvedinmanyprocessesin the body and affect the pathology of many diseases. Studies show that regulation of these metabolites could be a key innovation in the treatment of cance r, cardiovascular or neurodegenerative diseases. The methoxyindole pathway is another important tryptophan processingpathway.Itsbest - knownmetabolitesareserotonin,whichactsasaneurotransmitter, andmelatonin,ahormonewithimmunomodulatoryeffect sregulatedby thecircadianclock . This workdeals with thecircadian rhythmicityofenzymeexpressionofthesetwo metabolic pathways.Italsodescribestheeffectofsystemicadministrationoflipopolysaccharideendotoxin ontheexpressionofgenesoft heseenzymes.OurexperimentsusedWistarratsat30daysofage. The lipopolysaccharide was administered...
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MRI of Rats - Quantification of T1 in Myocardium
Vitouš, Jiří ; Mézl, Martin (referee) ; Jiřík, Radovan (advisor)
This thesis focuses on cardiac imaging and quantification of T1 relaxation time in rat hearts. Its main focus is to investigate available methods for such quantification and their application in the development of quantification tools. The large impact is given to methods of acquisition synchronization, mainly with respect to cardiac motion and breathing using retrospective gating, where the navigator signal is obtained solely from the acquired data, so without any external equipment such as the ECG or respiratory sensors. This paper takes into account situations where steady-state has been reached and also those where it has not, by means of contrast agent injection or by inversion pulses.
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Cardioprotective effect of adaptations to hypoxia and cold: Connexin 43 and hexokinase 2
Kohútová, Jana
Ventricular arrhythmias are the main cause of death worldwide. An increased incidence of arrhythmias in the heart of mammals is accompanied by a remodeling of the cellular distribution gap between the channels of mainly connexin 43 (Cx43). Recently has been demonstrated significant effect of mitochondria and their association with arrhythmogenesis. Various pathological conditions alter the expression and / or distribution of Cx43, depending on the phosphorylation status. but also on altering the association of hexokinase with mitochondria, which reduces the likelihood of apoptosis activation. Adaptation to intermittent hypobaric hypoxia potentiates endogenous pathways reducing the incidence of ventricular arteries, whereas continuous normobaric hypoxia does not have this effect. Another studied model is cold acclimatization, which has been known for several decades by known effects on human health. However, the heart study of these models in relation to Cx43 is missing. Our goal was to determine the expression of Cx43, phosphorylated Cx43 (p-Cx43) and hexokinase (HK1, HK2) and their distribution in cardiomyocytes. In addition, the expression of Cx43 upstream kinases, protein kinase A, protein kinase G, casein kinase 1 in normoxic and hypoxic left ventricles of rats, along with Cx43 distribution...
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The role of PGC-1α during the development of a cardioprotective phenotype in a rat adapted to mild cold
Bajsová, Barbora ; Žurmanová, Jitka (advisor) ; Szeiffová Bačová, Barbara (referee)
Cold exposure elicits a thermoregulatory response in an organism. If the cold stimulus is sufficient, there is increased heat generation by shivering thermogenesis. Under prolonged action of the cold stimulus, shivering thermogenesis is replaced by non-shivering thermogenesis. Non-shivering thermogenesis in the rat takes place predominantly in brown adipose tissue (BAT), where the uncoupling protein 1 (UCP1) is activated in mitochondria under the control of adrenergic signaling. The activity of UCP1 is crucial for heat production. The coactivator PGC-1α plays an important role in mitochondrial biogenesis and in the energy metabolism of BAT and heart, and its function is associated with cardioprotection. Recently, the cardioprotective effects of mild cold adaptation at 8±1 řC were discovered in our laboratory, which reduced the size of ischemia-reperfusion injury without negative side effects. However, the molecular nature of the events induced by adaptation to mild cold is unknown neither in BAT nor in the heart itself. Therefore, the aims of the thesis were 1) to characterize the development of BAT at the level of expression of selected proteins and mitochondrial markers during acute cold exposure and chronic cold adaptation with subsequent recovery and 2) to determine the role of PGC-1α and...
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