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Role of phospholipases A2 in the mechanism of cardioprotection induced by adaptation to chronic hypoxia
Míčová, Petra ; Novotný, Jiří (advisor) ; Kuda, Ondřej (referee) ; Kazdová, Ludmila (referee)
Cardiovascular diseases, particularly acute myocardial infarction, are the leading causes of death in developed countries including the Czech Republic. One of the ways to increase cardiac resistance against acute ischemia/reperfusion (I/R) injury is adaptation to chronic hypoxia. However, changes at the molecular level associated with this adaptation have still not been fully explored. It is obvious that the myocardial function depends on maintaining membrane integrity and cellular homeostasis of cardiomyocytes. From this perspective, phospholipases A2 (PLA2) are the key enzymes that take part in the remodeling and repairing of the cell membranes. Moreover, PLA2 are also involved in generation of lipid signaling molecules - free long chain fatty acids (FA) and 2-lysophopholipids. In myocardium, members of three major PLA2 classes are present: cytosolic PLA2 (cPLA2), calcium-independent PLA2 (iPLA2) and secretoric PLA2 (sPLA2). This thesis aimed to determine the following in the left ventricular myocardium of adult male Wistar rats: 1) The effect of intermittent hypobaric hypoxia (IHH; 8 hours/day, 5 days/week, 5 weeks, ~ 7000 m) on the expression of total cPLA2α and its phosphorylated form (p-cPLA2α, Ser505 ), and further iPLA2 and sPLA2IIA, as well as signaling proteins activating cPLA2α enzyme...
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Effect of chronic hypoxia on antioxidative capacity of rat myocardium.
Závišková, Kristýna ; Nováková, Olga (advisor) ; Žurmanová, Jitka (referee)
Adaptation to chronic hypoxia activates endogenous signaling cascades, which lead to cardiac protection against acute ischemia/reperfusion (I/R) injury. The molecular mechanism of this phenomenon has not been fully clarified yet. However, it was proved that reactive oxygen species (ROS) take part in cardioprotective signaling pathway inducted by chronic hypoxia. The high level of ROS must be precisely regulated by antioxidative system of a cell. The aim of diploma thesis was to examine the effect of intermittent hypobaric hypoxia (IHH, 7 000 m) on relative amount of antioxidative enzymes (peroxiredoxin 6 - PRX6, thioredoxin 1 and 2 - TRX1 and TRX2, thioredoxin reductase 1 - TRXR1) and also enzymes of iron metabolism (heme oxygenase 1 and 2 - HO1 and HO2, aconitase 1 and 2 - ACO1 and ACO2), which participate in regulation of cell redox state. Moreover, we studied the effect of adaptation to IHH and an antioxidant tempol on relative amount of calcium-independent phospholipase A2 (iPLA2). iPLA2 can remove peroxidized fatty acids from membrane phospholipids. On the other hand, iPLA2 can damage cell in I/R conditions. All enzymes were studied in homogenates from normoxic and IHH adapted rat left ventricular myocardium by Western blot. Adaptation to IHH caused a decrease of PRX6 and on the opposite an increase of...
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Role of oxidative stress in cardioprotection induced by exercise.
Kyclerová, Eva ; Nováková, Olga (advisor) ; Kašparová, Dita (referee)
Cardiovascular diseases are the major cause of death in developed countries. It is known that heart muscle can activates endogenous protective pathways in response to stress, thereby increasing resistance against ischemia/reperfusion (I/R) injury. Protective pathways involve many signaling molecules and reactive oxygen species (ROS) play an important role among them. ROS are applied in cardioprotection induced by various stimuli, such as chronic hypoxia, preconditioning and also physical exercise. It has been demonstrated that regular physical exercise naturally leads to the positive adaptation to protect heart against injury. The balance between production of ROS and their removal by antioxidant protection system is important for the right functioning of the heart. The overproduction of ROS occurs in pathological conditions such as an I/R leading to oxidative stress contributing to subsequent damage of heart. ROS may contribute not only to the injury but in the mild concentrations, resulting for example from physical exercise, ROS are important signaling molecules involved in series of events leading to cardioprotection. Slightly increased oxidative stress protects the heart by increasing the capacity of antioxidant system, stimulates angiogenesis, activates mitochondrial biogenesis and physiological...
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Aktivita antioxidačních enzymů za různých patofyziologických stavů.
Vávrová, Lucie ; Tvrzická, Eva (advisor) ; Borovanský, Jan (referee) ; Oliyarnyk, Olena (referee)
Background: Oxidative stress is supposed to be implicated in the pathogenesis of several diseases which are connected with increased formation of reactive oxygen and nitrogen species (RONS). Oxidative stress could play an important role in the pathogenesis of inflammation and sepsis, acute and chronic pancreatitis or in the development of cancer. Organisms are protected against RONS from antioxidant system that is composed of antioxidant enzymes and non-enzymatic antioxidants. To the most important antioxidant enzymes belong superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase, glutathione reductase and paraoxonase (PON). The aim of this Doctoral Thesis was to investigate the behaviour of three of these antioxidant enzymes - CuZnSOD, CAT and PON1 in different pathophysiological states. Materials and methods: The activities of CuZnSOD, CAT and PON1 were measured in six different pathophysiological states. Forty patients with metabolic syndrome (MetS), 35 women with depressive disorder (DD), 30 septic patients (SP), 50 patients with pancreatic cancer (PC), 50 patients with chronic pancreatitis (CP) and 13 patients with acute pancreatitis (AP) were included in different studies together with sex- and age-matched healthy controls (CON). Patients with AP and SP were observed in the course...
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Condition dependence of sexually selected ornaments in birds
Tomášek, Oldřich ; Albrecht, Tomáš (advisor) ; Verhulst, Simon (referee) ; Šálek, Miroslav (referee)
Sexual ornaments important for mating success in many species are often assumed to evolve as condition-dependent signals of individual quality. Ornament expression can be associated with age and survival, thereby signalling individual viability. Here, we have tested viability signalling function of tail streamers and their importance for within-pair and extra-pair fertilisation success in the European barn swallow (Hirundo rustica rustica). In contrast to previous studies on this subspecies, our data suggest that tail length is not associated with fertilisation success in our population. Instead, the most important predictors of within-pair and extra-pair fertilisation success were female and male age, respectively. Our data supported viability signalling function of male tail streamers, as documented by age-related within- individual increase in their length. There was no evidence for senescence in this trait. Contrary to some previous studies, the viability signalling function of tail streamers was further supported by observed selective disappearance of males with shorter tails. Several physiological mechanisms have been proposed as maintaining signalling honesty. Among them, oxidative stress from highly reactive species (RS), including free radicals, attracted a considerable attention. Given...
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Oxidative stress induced by iron and the influence of flavonoids and bisphosphonates
Kolek, Metoděj ; Eybl, Vladislav (advisor) ; Habermann, Vlastimil (referee) ; Hrdina, Radomír (referee)
Iron is an essential element for living organisms. However, as it is a transition metal, it can participate in Fenton reaction resulting in generation of free radicals and oxidative damage to tissues. Antioxidants may prevent possible iron toxicity by chelating free iron or scavenging free radicals. Falvonoids are naturally occurring substances that are capable of formation of complexes with metals, including iron. T h e y have been show to possess antioxidant activity, which depends on molecular complexity of numerous types of flavonoids, e.g. quercetin and silibinin. Bisphosphonates are synthetic drugs used to treat various metabolic diseases of bones. Their principál effect is an inhibition of osteclast activity leading to a decreased bone resorption. Bisphosphonates have been however shown to exert some antioxidant activity in in vitro experiments, too. The aim of this PhD thesis was to investigate the role of iron in toxicity of other metals (cadmium) and the effect of flavonoids (quercetin and silibinin) and bisphosphonates (clodronate, etidronate and risedronate) on iron-induced oxidative damage in vivo. Experiments were performed in male mice (CD-1, Charles River, 25-35 body weight). Iron was administered intraperitoneally or in the diet. Cadmium was administered subcutaneously. Flavonoids and...
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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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Effects of selected natural substances on the antioxidant system of an organism
Hodková, Anna ; Eybl, Vladislav (advisor) ; Mayer, Otto (referee) ; Anzenbacherová, Eva (referee)
of study named: Effects of selected natural substances on the antioxidant system of an organism Developed: Mgr. Anna Hodková Department of Pharmacology and Toxikology, Faculty of Medicine in Pilsen, Charles University in Prague Pilsen 2016 The aim of this study was to compare the effects of selected natural substances on the antioxidant defense system under comparable conditions, focusing on influencing the activity of selenoenzymes thioredoxin reductase (TrxR-1) and glutathione peroxidase (GPx-1). Experiments were performed in rats (Wistar, male). Livers, and in some cases kidneys were collected in all experiments. Homogenates were created from the collected organs and subsequently the activity of TrxR-1 and GPx-1, glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD), and reduced glutathione (GSH) and lipid peroxidation (LP) levels were determined. We demonstrated significant effects of selected natural substances on the redox system, including influences of selenoenzymes thioredoxin reductase and glutathione peroxidase. The biggest influence on the activity of selenoenzymes thioredoxin reductase and glutathione peroxidase had hydroxytyrosol (HT) and oleuropein (OLEU). In rat liver tissue there was a significant decrease of the activity of both above mentioned enzymes after...
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Activity of antioxidant enzymes in different pathophysilogical states.
Vávrová, Lucie
Background: Oxidative stress is supposed to be implicated in the pathogenesis of several diseases which are connected with increased formation of reactive oxygen and nitrogen species (RONS). Oxidative stress could play an important role in the pathogenesis of inflammation and sepsis, acute and chronic pancreatitis or in the development of cancer. Organisms are protected against RONS from antioxidant system that is composed of antioxidant enzymes and non-enzymatic antioxidants. To the most important antioxidant enzymes belong superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase, glutathione reductase and paraoxonase (PON). The aim of this Doctoral Thesis was to investigate the behaviour of three of these antioxidant enzymes - CuZnSOD, CAT and PON1 in different pathophysiological states. Materials and methods: The activities of CuZnSOD, CAT and PON1 were measured in six different pathophysiological states. Forty patients with metabolic syndrome (MetS), 35 women with depressive disorder (DD), 30 septic patients (SP), 50 patients with pancreatic cancer (PC), 50 patients with chronic pancreatitis (CP) and 13 patients with acute pancreatitis (AP) were included in different studies together with sex- and age-matched healthy controls (CON). Patients with AP and SP were observed in the course...
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