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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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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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Therapeutic drug monitoring in clinical practice and research
Ďuricová, Jana ; Grundmann, Milan (advisor) ; Mayer, Otto (referee) ; Vítovec, Jiří (referee)
Introduction: The human cytochrome P450 2D6 (CYP2D6) is involved in the oxidative metabolism of about 25 % of all commonly prescribed drugs. It is characterized by high range of interindividual variability due to both environmental and genetic factors. The ability to measure the activity of CYP2D6 enzyme is of high significance. Genotyping alone is not sufficient to accurately predict an individual's actual CYP2D6 activity, phenotyping on the other hand can determine the exact enzymatic activity as it also reflects non-genetic factors. Beta-blocker agent metoprolol undergoes extensive pre-systemic elimination, with enzyme CYP2D6 accounting for about 70 to 80 % of its metabolism. Metoprolol also serves as one of the probe drugs of CYP2D6. The metabolic ratio of metoprolol over its metabolite -hydroxymetoprolol in plasma 3 hours after metoprolol administration is used for the measurement of CYP2D6 enzyme activity. Aims: To compare CYP2D6 metabolic activity after first metoprolol dose and in steady state. Further to investigate the influence of CYP2D6 activity on metoprolol pharmacokinetics and pharmacodynamics in patients on metoprolol therapy. Methods: Thirteen adult hypertensive patients in whom an introduction of beta-blocker metoprolol was indicated were included for comparison of CYP2D6...
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