National Repository of Grey Literature 8 records found  Search took 0.00 seconds. 
Potential toxicity of terpenes and their effects in liver cells
Zárybnický, Tomáš ; Boušová, Iva (advisor) ; Anzenbacherová, Eva (referee) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Tomáš Zárybnický Supervisor: assoc. prof. PharmDr. Iva Boušová, Ph.D. Consultant: assoc. prof. Ing. Petra Matoušková, Ph.D. Title of Doctoral Thesis: Potential toxicity of terpenes and their effects in liver cells The public interest in herbal products, supplements, extracts or isolated active compounds has been increasing during last decades. The aim of this doctoral thesis was to study selected compounds from the group of monoterpenes and sesquiterpenes and their interactions with liver cells: interactions with drug metabolising enzymes, their potential liver toxicity and looking for novel mechanisms of action. The literature about hepatotoxic properties of several monoterpenes and sesquiterpenes, that showed liver toxicity, was summarized first. Then, the study was aimed toward a known hepatotoxicant (R)-pulegone and its presumed metabolite (R)- menthofuran. The toxicity results in precision-cut human liver slices have shown that (R)- menthofuran was less toxic to human liver and that the reason may be inter-species differences between human and mice. Several sesquiterpenes (farnesol, cis-nerolidol, trans-nerolidol, α-humulene, β-caryophyllene, and caryophyllene oxide) have previously...
Modulation of biotransformation and antioxidant enzymes by selected natural compounds
Lněničková, Kateřina ; Szotáková, Barbora (advisor) ; Anzenbacherová, Eva (referee) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Kateřina LNĚNIČKOVÁ Supervisor: prof. Ing. Barbora SZOTÁKOVÁ, Ph.D. Title of Doctoral Thesis: MODULATION OF BIOTRANSFORMATION AND ANTIOXIDANT ENZYMES BY SELECTED NATURAL COMPOUNDS Public interest in various dietary supplements containing herbs, herbal extracts or isolated active compounds has increased significantly over past decades. Consumption of these supplements increases worldwide and they are often consumed in unreasonably high doses, as they are generally considered as safe. Upon the intake to organism, these compounds are, as other xenobiotics, modified mostly by xenobiotic-metabolizing enzymes and they could influence these enzymes at the same time. Potential modulation of xenobiotic-metabolizing enzymes' activity (induction or inhibition) can seriously affect pharmacokinetics of concomitantly administered drugs. Knowledge of the possible impact of natural compounds on the xenobiotic-metabolizing enzymes is essential for their safe use. The aim of this doctoral thesis was to study the effects of selected herbal extracts and their active chemical constituents on the activity and expression of xenobiotic-metabolizing and antioxidant enzymes. We have focused on the study of effects of...
Metabolism, transport and anticancer effect of classical and novel taxanes
Václavíková, Radka ; Gut, Ivan (advisor) ; Perlík, František (referee) ; Anzenbacherová, Eva (referee)
L I I I I I I I I t CONCLUSIONS The dissertation thesis contributes to detail knowledge of the metabolism, transport and anticancer effects of classical taxanes (paclitaxel and docetaxel) as well as their novel synthetic analogs (SB-T-1103, SB-1'-1214 and SB-T-1216). The r]lost rmportanl reslrlts concerning studies on these anticancet drugs are srultnarized as iollorvs: o Detail metabolisrrr oť paclitaxel and docetaxel rvas estimated in human. rat. pig arrd minipig liver microsomes. The metabolism of docetaxel rvas the same i:r all four tested species. Drug rvas metabolized mainly to hydroxydocetaxel and two minor h1'droxyoxazol.idinones A and B. Despite various simiiarities between human and pig netabolism of paclitaxel, the profile oť paclitaxel metabolites in the studied species r'u.as different and main hunan metabolite óo.oHP renrains uniquelv human one' The other new metabolites of paclitaxel w.ere revealed. speciíicall1 di-oHP in ra1s and a new. hydroxypaclitaxel in rats. pigs and minipigs. q,here thrs metabolite is the main metabolic pathway oť paciitaxel. The major enzymes responsible for oxidative metaboiism of paclitaxei are CYP2CB and CYP3A4 in humans and CYP3Ai/2 in rats. Docelaxel is oxidatively metabolized by GYP3A famil"v in humans as rvell as in rats. The oxidation metabolism of classical...
Modulation of biotransformation and antioxidant enzymes by selected natural compounds
Lněničková, Kateřina ; Szotáková, Barbora (advisor) ; Anzenbacherová, Eva (referee) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Mgr. Kateřina LNĚNIČKOVÁ Supervisor: prof. Ing. Barbora SZOTÁKOVÁ, Ph.D. Title of Doctoral Thesis: MODULATION OF BIOTRANSFORMATION AND ANTIOXIDANT ENZYMES BY SELECTED NATURAL COMPOUNDS Public interest in various dietary supplements containing herbs, herbal extracts or isolated active compounds has increased significantly over past decades. Consumption of these supplements increases worldwide and they are often consumed in unreasonably high doses, as they are generally considered as safe. Upon the intake to organism, these compounds are, as other xenobiotics, modified mostly by xenobiotic-metabolizing enzymes and they could influence these enzymes at the same time. Potential modulation of xenobiotic-metabolizing enzymes' activity (induction or inhibition) can seriously affect pharmacokinetics of concomitantly administered drugs. Knowledge of the possible impact of natural compounds on the xenobiotic-metabolizing enzymes is essential for their safe use. The aim of this doctoral thesis was to study the effects of selected herbal extracts and their active chemical constituents on the activity and expression of xenobiotic-metabolizing and antioxidant enzymes. We have focused on the study of effects of...
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...
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...
The metabolic pathway arginine-nitric oxide and its pharmacological modulation in acute and chronic airway diseases
Havlínová, Zuzana ; Chládek, Jaroslav (advisor) ; Anzenbacherová, Eva (referee) ; Pávek, Petr (referee)
The first part of the theses describes the changes in the metabolic pathway of arginine- nitric oxide using a model of acute lung injury (ALI) induced by bacterial lipopolysaccharide (LPS) in Wistar rats. ALI was induced by i.p. or i.t. administration of 5 mg/kg LPS (Escherichia coli, serotype O55:B5). The observational period was terminated at 3, 6 and 24 hrs following the administration. After that, the expression was studied at mRNA and protein levels of inducible and endothelial NO synthases (eNOS, iNOS), arginase 1 and 2 (ArgI, ArgI), and of cationic amino acid transporters (CAT) in lung and liver tissue, Experimental work also included the monitoring of exhaled nitric oxide (eNO) and arginine concentrations in plasma and bronchoalveolar lavage fluid (BAL). The model was further characterized by biochemical markers, the indices of alveolo- capillary membrane permeability, the presence of inflammatory cells and the concentrations of oxidative and nitrossative stress markers in the airways. After i.p. injection of LPS, a profound increase occurred in exhaled eNO and NOx concentrations in BAL and plasma. The increase in eNO was observed already in 2 hr following LPS application and its maximum was >30fold above the controls. After i.t. application, there were signs of increased oxidative stress in...

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