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Glutathione and glutathione-dependent enzymes in various pathophysiological states.
Kodydková, Jana
Backround: Oxidative stress (OS) has been implicated in pathogenesis of human disorders such as depressive disorder, sepsis, cardiovascular disease, acute and chronic pancreatitis, and cancer. Increased OS is result of imbalance between increased reactive oxygen and nitrogen species (RONS) production and / or insufficient activity of antioxidant defence system. Antioxidant system, which is composed of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidases (GPX), glutathione reductase (GR) and non- enzymatic antioxidant reduced glutathione (GSH) plays an important role in the protection of cells against enhanced OS. The aim of this study was to assess the OS markers and antioxidant enzymes in different pathophysiological states. Materials and methods: Activities of erythrocyte glutathione peroxidase (GPX1), GR and concentration of GSH as well as levels of OS markers were analysed in six different pathophysiologic states. These parameters were measured in 35 women with depressive disorder (DD), 40 patients with metabolic syndrome (MetS), 30 septic patients (S) followed up in the course of sepsis; 15 non-septic critically ill patients (NC), 13 patients with acute pancreatitis (AP), 50 with chronic pancreatitis (CP) and 50 patients with pancreatic cancer (PC), compared to...
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Glutathion a glutathion dependentní enzymy za různých patofyziologických stavů.
Kodydková, Jana ; Tvrzická, Eva (advisor) ; Kazdová, Ludmila (referee) ; Vejražka, Martin (referee)
Backround: Oxidative stress (OS) has been implicated in pathogenesis of human disorders such as depressive disorder, sepsis, cardiovascular disease, acute and chronic pancreatitis, and cancer. Increased OS is result of imbalance between increased reactive oxygen and nitrogen species (RONS) production and / or insufficient activity of antioxidant defence system. Antioxidant system, which is composed of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidases (GPX), glutathione reductase (GR) and non- enzymatic antioxidant reduced glutathione (GSH) plays an important role in the protection of cells against enhanced OS. The aim of this study was to assess the OS markers and antioxidant enzymes in different pathophysiological states. Materials and methods: Activities of erythrocyte glutathione peroxidase (GPX1), GR and concentration of GSH as well as levels of OS markers were analysed in six different pathophysiologic states. These parameters were measured in 35 women with depressive disorder (DD), 40 patients with metabolic syndrome (MetS), 30 septic patients (S) followed up in the course of sepsis; 15 non-septic critically ill patients (NC), 13 patients with acute pancreatitis (AP), 50 with chronic pancreatitis (CP) and 50 patients with pancreatic cancer (PC), compared to...
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Glutathione and glutathione-dependent enzymes in various pathophysiological states.
Kodydková, Jana
Backround: Oxidative stress (OS) has been implicated in pathogenesis of human disorders such as depressive disorder, sepsis, cardiovascular disease, acute and chronic pancreatitis, and cancer. Increased OS is result of imbalance between increased reactive oxygen and nitrogen species (RONS) production and / or insufficient activity of antioxidant defence system. Antioxidant system, which is composed of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidases (GPX), glutathione reductase (GR) and non- enzymatic antioxidant reduced glutathione (GSH) plays an important role in the protection of cells against enhanced OS. The aim of this study was to assess the OS markers and antioxidant enzymes in different pathophysiological states. Materials and methods: Activities of erythrocyte glutathione peroxidase (GPX1), GR and concentration of GSH as well as levels of OS markers were analysed in six different pathophysiologic states. These parameters were measured in 35 women with depressive disorder (DD), 40 patients with metabolic syndrome (MetS), 30 septic patients (S) followed up in the course of sepsis; 15 non-septic critically ill patients (NC), 13 patients with acute pancreatitis (AP), 50 with chronic pancreatitis (CP) and 50 patients with pancreatic cancer (PC), compared to...
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Biotransformation aspects on novel carbocyclic nucleoside analogs.
Rozumová, Nela ; Mertlíková Kaiserová, Helena (advisor) ; Rumlová, Michaela (referee)
Carbocyclic nucleoside analogs with norbornane moiety that have been synthesized at IOCB AS CR, represent new potential chemotherapeutic agents with significant activity against Coxsackieviruses. The main objective of this work was to study the metabolism and mechanism of action of the original analog carbocyclic nucleoside MS 254, which is characterized by its antiviral and cytostatic effects. The attention was partially paid also to the two structurally related substances (MS 255, MS 320). In this work, we determined cytotoxicity of these compounds in cell culture and the effect of MS 254 on the amount of total and oxidized glutathione, activity of glutathione-S-transferase (GST), glutathione reductase (GR) and the effect on cellular oxidative stress. The kinetics of the conjugation of MS 254 by human GST was also studied. It was found that of the three substances tested MS 255 was the most cytotoxic and MS 254 was the least cytotoxic compound. It was further found that MS 254 does not cause significant oxidative stress and that it increases the activity of GST and GR in a dose-dependent manner. Michaelis-Menten constant of the conjugation of MS 254 with the glutathione (main metabolic pathway) was determined in the milimolar range, indicating a relatively low affinity of MS 254 for GST.
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