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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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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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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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