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Dissertations / Theses on the topic 'Xenobiotik'

Author: Grafiati

Published: 4 June 2021

Last updated: 1 February 2022

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1

Píšťková, Veronika. "Studium průběhu degradace xenobiotik a biologicky aktivních látek s využitím oxidu titaničitého." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2012. http://www.nusl.cz/ntk/nusl-216860.

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Heterogenous photocatalysis using titanium dioxide seems to be a promising method for disposal xenobiotics from the environment. The aim of this diploma thesis is the study of degradation of selected xenobiotics and biologically active substrances applying this method. Theoretical part of diploma thesis deals with the principals of heterogenous photocatalysis by means of a semiconductor TiO2 and the examples of its possible application are mentioned too. The compounds which could be appropriate for a study of degradation were selected from the group of pharmaceuticals and pesticides. The properties of target substances and their environmental impact were described. Furthermore, a bibliographic search focused on the possibilities of their analytical determination was conducted. The experimental part of the thesis describes the experiments with photocatalyst in a form of powder as well as with immobilized photocatalyst in thin layer on a carrier. Identification and quantification of analytes was realized by high performance liquid chromatography with mass spectrometic detection.

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2

Dobre, Cristina. "Vitamin E vid prostatacancer." Thesis, Umeå universitet, Farmakologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-121398.

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Sammanfattning Vitamin E är en substans med antioxidanta egenskaper, ett fettlösligt vitamin som kan finnas i naturliga källor såsom vegetabiliska oljor, ägg, grönsaker, spannmål, frukter,kött men också i syntetisk form. I dagsläget är vitamin E också tillgängligt som kosttillskott och används förebyggande och/eller vid behandling av sjukdomar som kardiovaskulära sjukdomar, arterioskleros, diabetes mellitius samt olika former av cancer. Vid intag av vitamin E kan oxidativ stress minskas vilket produceras av fria radikaler (t.ex. joniserande strålning, giftiga föreningar från luft, vatten, mat) som drabbar celler och på det sättet förebyggs och fördröjs uppkomst av sjukdomar. Utöver sin antioxidant effekt och är vitamin E involverat i immunförsvaret, cellsignalering,genreglering samt andra metaboliska processer. Dessa egenskaper har gjort av vitaminE är en intressant kandidat till utredning vid prostatacancer (adenocarcinom), som är den vanligaste tumörformen i Sverige hos män över 50-års ålder. Denna litteraturstudie har för syfte att undersöka det empiriska stödet för tesen omvitamin E kan ha en förebyggande effekt mot prostatacancer och vilka risker som finns vid intag av vitamin E vid prostatacancer. Tidigare forskning har visat att det har enantioxidativ inverkan på kroppens organ och det har därför funnits en tro på att den kan hjälpa förebygga prostatacancer. Litteraturstudien bygger på originalartiklar framförallt från PubMed, Socialstyrelse hemsidan, WebMd, olika medicinska böcker och i Google med sökord som: vitamin E, prostatacancer, tokoferol och prostatacancer,oxidative stress, antioxidant, androgen metabolism och vitamin E, prostatacancer ocharv, androgen och vitamin E. Resultatet av studierna visar att det inte finns ett entydigt empiriskt stöd för att vitaminE (tokoferol) har en förebyggande effekt mot prostatacancer. Vissa studier visar ett stöd för att det finns en förebyggande effekt, andra visar att det inte finns ett stöd och en visar en signifikant ökad risk för prostatacancer vid intag av tokoferol. Prostatacancer kan inte förebyggas med vitamin E (tokoferol) enligt forskningsresultaten i denna studie. Vidare forskning krävs för att se om det kan finnas kombinationer med t.ex. selen för att öka effektiviteten för att förebygga prostatacancer.

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3

Mravcová, Ludmila. "Využití separačních technik na bázi plynové a kapalinové chromatografie s různým typem detektorů pro stanovení biologicky aktivních látek a vybraných xenobiotik." Doctoral thesis, Vysoké učení technické v Brně. Fakulta chemická, 2011. http://www.nusl.cz/ntk/nusl-233330.

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This work deals with the using and application of separation techniques for analysis of polymers degradation and polycyclic aromatic hydrocarbons. Thereby this work is separated to two special parts. In the first part, the degradation properties of synthetic biopolymers based on lactic acid, gylcolic acid and poly(ethyleneglycol) PLGA-PEG-PLGA and ITA-PLGA-PEG-PLGA-ITA (modified by itaconic acid) were studied. These copolymers (firstly their thermosensitive hydrogels) should be used for therapy of fractures in orthopedy (as adhesives). Therefore, the sol-gel and gel-sol phase diagrams were determinated for selected samples of copolymers. The samples forming gel at 37 C was used for other study. Polymer samples were depredated in phosphate buffer at 37°C. The degradation process of physical hydrogels was described by the decrease of molecular weight and the increase of concentration lactic acid and glycolic acid in phosphate buffer. The obtained results confirmed that the degradation of polymer modified by itaconic acid is faster process than no modified polymer and polymers with lower ratio PLGA/PEG degrade also faster than lower ration PLGA/PEG. The influence of pH it was also tested. The rate of degradation of polymers was follow pH 4,0

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4

Turková, Lucie. "Porovnání sekvenčních variant genů pro biotransformační enzymy u různých typů karcinomů." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2017. http://www.nusl.cz/ntk/nusl-295694.

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Xenobiotic biotransformation process and its capacity is crucial for xenobiotic chemicals elimination that may cause damage toward cell structures. The effectiveness of the enzymes included in this process depends on the gene variants that encodes them. The aim of this work was to compare certain polymorphisms of selected genes between cases and control groups. Studied polymorphisms were null genotypes of the glutathione S-transferase gene M1 and T1 and the insertion of TA dinucleotide in the promotor region of UDP-glucuronosyl transferase 1A1. The number of cases group was six included patients with colorectal, lung, prostate, breast, pancreatic and head and neck cancer. Total number of analysed individuals was 1 118 for cancer cases and 470 for healthy controls. The control group was divided into two groups, the first one was called general and the second one was called special included healthy individuals with no cancer history in their closest family members. Gilbert syndrome (GS) is caused by homozygous insertion of the TA dinucleotide in the TATA box of the gene UGT1A1 and it causes elevated bilirubin levels. Bilirubin is a potent antioxidant in human body, so the aim was to attest its protective effect toward cancer. We expected lower frequency of GS as a protective factor in the cases groups compared with controls. This hypothesis was confirmed in the breast cancer group (GS frequency 10,0 %) and pancreatic cancer group (GS frequency 11,1 %). In the general and special control groups the frequency of GS was 16,0 % and 15,4 % respectively. Although the other case groups show lower frequency of GS, the results weren´t statistically significant. Null GSTM1 genotype was observed with 50,4 % frequency in the general control groups and with 55,3 % frequency in the special control group. Neither the one of the cases groups hasn´t showed significantly lower percentage of null genotype. Despite expectation we observed statistically significant lower frequency of null genotype in the group of lung and pancreatic cancer group (37,4 % and 39,3 % respectively). According to this study, we can say that the lack of glutathione S-transferase M1 activity is not a risk factor for cancer development. Null genotype of GSTT1 wasn´t identified in both control groups at all. In case groups of breast and prostate cancer, there was only one individual carrying the null GSTT1 genotype. Statistically significant higher frequency of this polymorphism was observed in patients with colorectal cancer (9,7 %), lung cancer (17,2 %), pancreatic cancer (3,0 %) and head and neck cancer (15,9 %). In these groups the lack of glutathion S-transferase T1 activity might be considered as risk factor for cancer development. Nevertheless, for further verification it needs to take more investigation in this field, especially enlarge the number of patient in the case groups of head and neck, lung and pancreatic cancer.

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5

Adams, Samuel E. "Molecular similarity and xenobiotic metabolism." Thesis, University of Cambridge, 2010. https://www.repository.cam.ac.uk/handle/1810/225225.

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MetaPrint2D, a new software tool implementing a data-mining approach for predicting sites of xenobiotic metabolism has been developed. The algorithm is based on a statistical analysis of the occurrences of atom centred circular fingerprints in both substrates and metabolites. This approach has undergone extensive evaluation and been shown to be of comparable accuracy to current best-in-class tools, but is able to make much faster predictions, for the first time enabling chemists to explore the effects of structural modifications on a compound’s metabolism in a highly responsive and interactive manner. MetaPrint2D is able to assign a confidence score to the predictions it generates, based on the availability of relevant data and the degree to which a compound is modelled by the algorithm. In the course of the evaluation of MetaPrint2D a novel metric for assessing the performance of site of metabolism predictions has been introduced. This overcomes the bias introduced by molecule size and the number of sites of metabolism inherent to the most commonly reported metrics used to evaluate site of metabolism predictions. This data mining approach to site of metabolism prediction has been augmented by a set of reaction type definitions to produce MetaPrint2D-React, enabling prediction of the types of transformations a compound is likely to undergo and the metabolites that are formed. This approach has been evaluated against both historical data and metabolic schemes reported in a number of recently published studies. Results suggest that the ability of this method to predict metabolic transformations is highly dependent on the relevance of the training set data to the query compounds. MetaPrint2D has been released as an open source software library, and both MetaPrint2D and MetaPrint2D-React are available for chemists to use through the Unilever Centre for Molecular Science Informatics website.

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6

Smith, Nicola Jane. "Modulation of xenobiotic metabolism by garlic." Thesis, Liverpool John Moores University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247381.

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7

Tyzack, Jonathan David. "Prediction of cytochrome P450 xenobiotic metabolism." Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708289.

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8

Stříteský, Luboš. "Využití oxidačních procesů (AOP) pro odstraňování mikropolutantů." Master's thesis, Vysoké učení technické v Brně. Fakulta stavební, 2013. http://www.nusl.cz/ntk/nusl-226161.

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This thesis deals with advanced oxidation processes (AOPs) and it’s use for removal of micropollutants from wastewater. The first chapter explains the need AOPs, water quality, pollution and substances that are present in the water. Further, the first chapter outlines approach of the current legislation to micropollutants. The second chapter explains the theory and principle of operation of AOPs. This chapter is divided into two sections. The first section describes AOPs, which were tested at selected WWTP. In the second section, there are described some other AOPs. The third chapter is a literature retrieval of AOPs dealing with the removal of micropollutants. This chapter is focused on the removal of hormones by AOPs using ozone-based AOPs. The fourth chapter describes the actual testing of selected AOPs. The chapter describes selected WWTP, pilot-scale AOP unit and test results. In the last chapter there is designed and described full-scale AOP tertiary unit for removing of micropollutants. The last chapter also contains economic analysis of the proposed tertiary unit.

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9

Munro, D. Ross. "Biphasic fermentation of xenobiotics." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq20681.pdf.

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10

Haselden, John Neil. "The synthesis and metabolism of xenobiotic acylglycerols." Thesis, Imperial College London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243552.

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11

Jones, Huw. "Xenobiotic metabolism and zebrafish (danio rerio) larvae." Thesis, University of Birmingham, 2010. http://etheses.bham.ac.uk//id/eprint/886/.

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There is a requirement for the characterisation of the metabolism of xenobiotics in zebrafish larvae, due to the application of this organism to toxicity testing and ecotoxicology. Genes similar to mammalian cytochrome P450 (CYP) 1A1, CYP2B6, CYP3A5 and UDP-lucuronosyl-transferase (UGT) 1A1 were demonstrated to be expressed during normal embryonic development, with increased expression post hatching in Wik strain zebrafish larvae (72 hours post fertilisation, hpf). Activities towards ethoxy-resorufin, 7-ethoxy-coumarin and octyloxymethylresorufin, using an in vivo larval assay, were also detected in 96 hpf Wik strain zebrafish larvae, indicative of oxidative and conjugative metabolism. The expression of the identified genes was modulated upon exposure to Aroclor 1254, and the metabolic activities towards ethoxy-resorufin, 7-ethoxy-coumarin and octyloxymethylresorufin were observed to be inducible by exposure to in vitro inhibitors of CYP activities. Wik strain zebrafish larvae (72 hpf) were also demonstrated to metabolise the pharmaceuticals acetaminophen and ibuprofen by oxidative and conjugative processes using liquid chromatography mass spectrometry and scintillation counting. Finally, the organic solvents dimethyl-sulfoxide and methanol were observed to reduce the expression of CYP and UGT genes, and the metabolism of ethoxy-resorufin, after 24 hours exposure to \(\leq\)0.1% volume/volume concentrations of the two solvents. It is suggested that these inhibitory effects are in part due to a reduction in the expression of the aryl hydrocarbon receptors, which are known regulators of drug metabolism genes. Overall the expression of genes and enzymatic activities similar to the mammalian drug metabolism genes have been demonstrated in Wik strain zebrafish larvae (96 hpf), and the first examples of the metabolism of pharmaceuticals by zebrafish larvae are also demonstrated. The modulation of the metabolism of xenobiotics by organic solvents suggests that caution must be exercised when interpreting data from toxicity tests when high solvent concentrations are applied to zebrafish larvae. The continued use of zebrafish larvae as a toxicity testing model is strengthened by the findings of this work.

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12

Smith, Gillian. "Xenobiotic regulation of cytochrome P450 gene expression." Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/20797.

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Cytochromes P450 (P450) are a ubiquitous class of monooxygenases located in the endoplasmic reticulum of mammalian cells. These enzymes catalyse the Phase I oxidative metabolism of a wide range of structurally diverse chemicals resulting in increased hydrophilicity and excretion. Certain chemicals are, however, metabolically activated by cytochrome P450, leading to the formation of cytotoxic and/or carcinogenic metabolites. This has been exploited in the design of many prodrugs, including anti-tumour agents, which are inactive as administered but become active in vivo following metabolism by one or more of the P450 isozymes. The regulation of P450 gene expression has been well documented in experimental animals, but at present there is very little information available about the regulation of human P450 genes, particularly in extra-hepatic tissues. Regulation of P450 expression by a range of xenobiotics, known to have profound effects on the expression of rodent P450 genes, has been studied in a mouse model and in cultured cells. Of particular interest were the potent and pleiotropic effects on murine P450 expression of TCPOBOP (1,4 bis [s,(3,5-dichloropyridyloxy)] benzene), which showed marked tissue and species specificity in its inductive effects in rodents. A model was developed, using human tumours grown as xenografts in immune deficient mice, in which the in vivo regulation of human P450 genes could be examined. TCPOBOP was shown to be equally effective at influencing human P450 gene expression and, in most cases, the patterns of gene regulation observed in experimental animals were also seen in the human tumours. These studies suggest that modulation of intra-tumour P450 levels by agents such as TCPOBOP may lead to enhanced metabolism of anticancer drugs such as cyclophosphamide, which require P450-mediated activaion in order to exert their anti-tumour effects.

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13

McCormick, David John. "The identification and synthesis of xenobiotic kairomones." Thesis, Manchester Metropolitan University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.237730.

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14

Benndorf, Dirk. "Molekulare Mechanismen der Resistenz von Bakterien gegenüber Xenobiotika /." Leipzig ; Halle : UFZ, 2000. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=009223329&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.

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15

Alexandrie, Anna-Karin. "Significance of polymorphisms in human xenobiotic metabolising enzymes /." Stockholm, 2002. http://diss.kib.ki.se/2003/91-7349-421-6/.

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16

James, V. J. "Regulation of xenobiotic catabolism in plant tissue culture." Thesis, Cardiff University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380205.

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17

Downie, Andrew L. "Xenobiotic metabolism in 'Arabidopsis thaliana' and 'Oryza sativa'." Thesis, University of Reading, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430922.

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18

Clark, Ian Paul. "Treatment studies on a xenobiotic containing industrial effluent." Thesis, University of Birmingham, 1990. http://etheses.bham.ac.uk//id/eprint/1397/.

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19

Rodriguez, Alvaro A. "Bio-inspired Toxicity Assay Based on Xenobiotic Metabolism." University of Akron / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=akron1333760056.

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20

Cikutovic, Salas Marcos A. "Pathologies in earthworms: sublethal biomarkers of xenobiotic toxicity." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc798085/.

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This research is part of an overall program to develop and use a suite of acute and sublethal toxicity biomarkers, and testing protocols for use in assaying potential effects of complex mixtures of xenobiotics such as found in soils containing agricultural biocides and petrochemical wastes dredged sediments, and hazardous waste sites (HWS). The purpose of this study was to evaluate four biomarkers of sublethal pathology that could be used in an integrative model of multiple toxicity endpoints with the earthworm Lumbricus terrestris.

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21

Hukkanen, J. (Janne). "Xenobiotic-metabolizing cytochrome P450 enzymes in human lung." Doctoral thesis, University of Oulu, 2000. http://urn.fi/urn:isbn:9514258649.

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Abstract The cytochrome P450 (CYP) enzyme system in human lung is an essential component in the pulmonary carcinogenicity of several inhaled xenobiotic compounds. The aim of this study was to elucidate the expression and regulation of xenobiotic-metabolizing CYP enzymes in human lung. To evaluate which of the two is a better surrogate cell model for lung tissue, the expression patterns of CYP enzymes in alveolar macrophages and peripheral blood lymphocytes were clarified by reverse transcriptase-polymerase chain reaction (RT-PCR) and compared to the expression in lung tissue. The pattern of CYP expression in alveolar macrophages was found to closely resemble the expression pattern in human lung tissue, while the pattern in lymphocytes was markedly different. The expression of CYP2B6, CYP2C, CYP3A5, and CYP4B1 mRNAs in alveolar macrophages was demonstrated for the first time. To facilitate mechanistic studies on human pulmonary CYP induction, the A549 lung adenocarcinoma cell line was characterized by RT-PCR, and the CYP expression pattern was found to compare reasonably well to human lung epithelial cells. The induction of CYP1A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) behaved as predicted, and CYP1B1 and CYP3A5 were also inducible by TCDD and dexamethasone, respectively. TCDD elevated the level of CYP1A1 mRNA (56-fold), while the induction of CYP1B1 mRNA was more modest (2.5-fold). The tyrosine kinase inhibitor genistein and the protein kinase C inhibitor staurosporine blocked CYP1A1 induction by TCDD, but did not affect CYP1B1 induction. The serine/threonine protein phosphatase inhibitor calyculin A and okadaic acid enhanced CYP1B1 induction slightly, but did not alter CYP1A1 induction. The expression of CYP3A forms in human pulmonary tissues was studied with RT-PCR and immunohistochemistry, and both methods established CYP3A5 as the main CYP3A form. CYP3A4 was expressed in only about 20% of the cases. In A549 cells, CYP3A5 was induced about 4-fold by the glucocorticoids budesonide, beclomethasone dipropionate, and dexamethasone. Maximal induction was achieved by concentrations as low as ~100 nM, suggesting that CYP3A5 could be induced in vivo in patients using inhaled glucocorticoids. However, there were no differences in CYP3A5 expression in alveolar macrophages in current glucocorticoid users, ex-users, and non-users. Cigarette smoking had a marked decreasing effect on CYP3A5 levels in alveolar macrophages. The presence and possible induction of CYP3A5 by glucocorticoids in human lung could have consequences for the maintenance of physiological steroid hormone balance in lung and the individual susceptibility to lung cancer of patients using glucocorticoids.

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22

Werner, Anett, Thomas Bley, Justus Wick, and Ralf Hauser. "XENOKAT – Biofilter für Xenobiotika in der Ressource Wasser." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-215206.

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Aus der Einleitung: "Xenobiotika werden durch den Menschen in die Stoffkreisläufe der Natur eingebracht, sie sind dort ursprünglich nicht anzutreffen. Dazu zählen auch Medikamente, die der menschliche Körper in kurzer Zeit wieder ausscheidet ohne diese abzubauen. Die bestehenden Abwasserreinigungsanlagen sind derzeit nicht in der Lage diese Frachten vollständig zu eliminieren, sodass sie unweigerlich in die Umwelt gelangen und dort undefiniert Einfluss nehmen. Xenobiotika können bereits in den großen Wasserreservoirs der Erde detektiert werden, die Prognose für die nächsten Jahre zeigt eine 30% Steigerung der Emissionen auf. In Deutschland gelangen z.B. jährlich 63 Tonnen des Schmerzmittels Diclofenac in die Flüsse (Bundesumweltamt 2014). Der Mensch hinterlässt regelrechte anthropogene Fußabdrücke, bestehend aus Schmerzmitteln, Antibiotika und Hormonen. Die problematischen Emissionen einiger Xenobiotika treten anhand von Folgeerscheinungen weltweit immer gravierender zutage (Bundesumweltamt 2014). So müssen das globale Artensterben (Geier in Indien), die Verweiblichung von Tierpopulationen in aquatischen Systemen und Krebserkrankungen mit partiell hohen Xenobiotika-Belastungen in der Umwelt in Zusammenhang gebracht werden. Die Entfernung von Xenobiotika insbesondere aus den Wasserkreisläufen stellt eine große ökonomische als auch ökologische Herausforderung zum Schutz der Lebensräume dar. ..."

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23

Pääjärvi, Gerd. "Xenobiotics-induced phosphorylations of MDM2 /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-951-3/.

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24

Colquhoun, K. O. "Microbial degradation of xenobiotics chemicals." Thesis, Nottingham Trent University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383652.

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25

Otto, Diana M. E. "Polychlorinated biphenyl (PCB) alterations of antioxidant defenses and xenobiotic metabolism in teleost fish: Role of tissue glutathione metabolism in xenobiotic detoxication pathways." Thesis, University of Ottawa (Canada), 1996. http://hdl.handle.net/10393/10074.

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Polychlorinated biphenyls (PCBs) are ubiquitously distributed in the aquatic and terrestrial environments, even though their production was stopped more than 20 years ago. The biochemical effects of PCBs are primarily initiated by the induction of drug metabolizing enzymes, especially cytochromes P450. In the first instance, these enzymes detoxify xenobiotics such as PCB congeners to facilitate their excretion from the animal. However, these processes are also known to generate more toxic metabolites, including the production of reactive oxygen species (ROS) which impact on cellular antioxidant defenses. Teleost fish contain an active endogenous antioxidant defense system, which consists of superoxide dismutase, catalase and the glutathione system. Apart from its antioxidant functions, glutathione (GSH) plays a major role in electrophilic conjugation of lipophilic conjugation (initiated by glutathione S-transferase, GST) and in the maintenance of cellular homeostasis. This thesis investigated the responses of drug metabolizing enzymes and endogenous antioxidant defenses in teleosts exposed to PCBs. The first field study showed that feral brown bullheads, harvested from the St. Lawrence River and contaminated with PCBs, had enhanced activities of ethoxyresorufin O-deethylase (EROD), a cytochrome P4501A (CYP1A) catalytic activity. GST activities were induced several fold in these River bullheads, which suggested active detoxication via GSH conjugation, although at the expense of tissue GSH content. A second field study involved the caging of hatchery reared rainbow trout at a PCB contaminated site. The trout showed significant accumulation of PCB congeners in skeletal muscle in the absence of changes in tissue drug metabolizing enzymes and antioxidant defenses. Endogenous antioxidant defenses were examined in rainbow trout and black bullheads. These systems were found to underlie age- and/or maturation-dependent changes. In a series of experiments, exogenous GSH was noted to serve as an efficient delivery agent of GSH to tissues in teleosts. This observation suggests that piscine GSH biochemistry differs from that of mammals, which respond poorly to exogenous GSH. This unique characteristic of the piscine GSH system could be important for fish husbandry while providing an interesting tool to study the biochemical effects of PCBs. A series of experiments found that a 3 day exposure of rainbow trout to 3,3$\sp\prime$,4,4$\sp\prime$-tetrachlorobiphenyl (TCB) had little impact upon tissue antioxidant defenses, while a 6 week exposure resulted in significant induction of activities of the conjugation enzyme UDP-glucuronosyltransferase, antioxidant enzymes activities and GSH levels in hepatic and extrahepatic tissues. However in both experiments TCB induced CYP1A metabolism. Additional experiments attempted to characterize to what extent tissue glutathione status influences basal and TCB induced hepatic CYP1A metabolism. Manipulation of tissue GSH content by either depletion (induced by L-buthionine- (S,R) -sulfoximine, BSO) or supplementation with pro-GSH agents (GSH and lipoate) revealed that glutathione status modified cytochrome P4501A at two stages, the CYP1A mRNA expression and the catalytic activity. This apparent cross-talk between the glutathione and cytochrome P450 systems suggested that glutathione homeostasis plays a major role in PCB induced metabolic alterations.

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26

Klumpp, Karoline [Verfasser]. "Interaktion zwischen verschiedenen Vitamin-D-Metaboliten und Mechanismen zur Metabolisierung und Elimination von Xenobiotika bei der RatteInteraction between different vitamin D metabolites and mechanisms for metabolism and elimination of xenobiotics in rats / Karoline Klumpp." Hannover : Stiftung Tierärztliche Hochschule Hannover, 2018. http://d-nb.info/1177951436/34.

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27

Hoffmann, Michael [Verfasser]. "Xenobiotika: Interaktionen und Alterationen im humanen Metabolismus / Michael Hoffmann." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1079840974/34.

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28

Williams, Delyth Einir. "Xenobiotic metabolism in skin and the effect of age." Thesis, Cardiff University, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395694.

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29

Clark, Nicholas William Edward. "Cutaneous xenobiotic metabolism and its role in percutaneous absorption." Thesis, University of Newcastle Upon Tyne, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317857.

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30

Spellman, Ellen Frances. "Xenobiotic metabolism by cytochrome P450 enzymes in the brain." Thesis, University of Sheffield, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247239.

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31

Chinn, Leslie W. "Pharmacodynamic effects of xenobiotic ABC transporters in peripheral tissues." Diss., Search in ProQuest Dissertations & Theses. UC Only, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3318516.

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32

Cheema, Manraj Singh. "Xenobiotic-dependent regulation of human karyopherin A2 (KPNA2) gene." Thesis, University of Surrey, 2011. http://epubs.surrey.ac.uk/843116/.

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A common reaction to xenobiotic exposure is the modulation of genes that mediate the response to such insult, including the drug metabolising enzymes and drug transporters. This transcriptional response is typically mediated by the nuclear receptor family of ligand activated transcription factors, and the translocation of these key regulators into the nucleus, whether before or after ligand binding, is a pre-requisite for their activity. The karyopherin a family of adapter proteins (6 in man) form a molecular bridge between nuclear cargoes and the nuclear import machinery. Previous work demonstrated that the rat karyopherin a genes are themselves responsive to a number of xenobiotics, including classical nuclear receptor ligands. The aim of this study was to delineate the molecular mechanism underlying transcriptional regulation of human karyopherin a2 (KPNA2) gene. In silico analysis of the 2.6kb immediately upstream and including the first exon of human KPNA2 promoter revealed several putative transcription factor binding sites, most notably for the nuclear receptors vitamin D receptor (VDR), progesterone receptor (PR), retinoid related orphan receptor a (RORa), peroxisome proliferated activated receptor a (PPARa), glucocorticoid receptor a (GRa), pregnane X receptor (PXR) and hepatic nuclear factor 4 (HNF4) and the anti-oxidant response protein, Nrf2. Using a reporter gene assay in the human hepatoma cell line Huh7, preliminary experiments demonstrated that the KPNA2 gene was responsive to cognate ligands for many of these nuclear receptors, as well as oxidative stress-mediated activation of Nrf2. In-depth analysis including promoter deletion, site directed mutagenesis and electrophoretic mobility shift assay were carried out to determine the molecular mechanism underlying these transcriptional effect. The down-regulation of human KPNA2 expression by cyproterone acetate was mediated via GRa and not PXR whereas the down-regulation of human KPNA2 expression by Wy-14,643 was elicited not by its cognate nuclear receptor, PPARa but most likely via Nrf2 through the oxidative stress signaling pathway. In conclusion, these findings provide a rational explanation for the mechanistic basis of human KPNA2 gene regulation by a number of endobiotics and xenobiotics, and postulate the importance of this phenomenon for optimizing cellular response to these stimuli.

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Prisažný, Adam. "Strukturní aspekty interakce huminových látek s iontovými organickými xenobiotiky." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2021. http://www.nusl.cz/ntk/nusl-449371.

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This diploma thesis was focused on studying the interaction of humic substances with ionic organic xenobiotics and its structural aspects. The method was chosen from my bachelor thesis, steady-state fluorescence spectroscopy, which is suitable for substances with weak fluorescence. The results showed that the interaction between humic acids and representatives of ionic organic xenobiotics (Septonex) was reflected in fluorescence quenching of humic acids and the shift of emission maximum to lower wavelength, hypsochromic (blue) shift. From the measurement results, we can assume that the interaction that is formed between the aromatic structures in humic acids and Septonex could be -cation interaction.

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Doušová, Petra. "Monitoring kontaminace lovné zvěře xenobiotiky na bázi organohalogenovaných sloučenin." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2010. http://www.nusl.cz/ntk/nusl-216631.

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Various animal or vegetable origin bio-indicators are used for the assessment of the environmental contamination. The wild animals were chosen for monitoring of xenobiotic based organohalogen compounds. The district health facility staff collected the samples of wild boars in the territory of Central Bohemia. The controlled substances were isolated from the matrix by an extraction. The extraction was made by a petrolether and then it was purified by a column chromatography. A final cleansing of the extract was made by an acid hydrolysis. The determination of the selected analytes was finished by the method of gas chromatography with an electron capture detector. The results gave us basic information about the wild boar contamination of organohalogen pollutants.

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35

Subramanian, Venkataramanan. "Functional Genomics of Xenobiotic Detoxifying Fungal Cytochrome P450 System." University of Cincinnati / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204753142.

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36

McKay, Judith A. "The expression of xenobiotic metabolising enzymes in human tumours." Thesis, University of Aberdeen, 1996. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU078740.

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The cytochromes P450 (CYPs), epoxide hydrolases (EHs) and glutathione S-transferases (GSTs) are three of the major families of enzymes involved in the metabolism of xenobiotics in the human body. Immunohistochemical analysis revealed a high frequency of expression of xenobiotic metabolising enzymes in all tumour types studied, in contrast to corresponding normal tissue which displayed only low levels of expression. Further examination of the CYP1 family was carried out by immunoblot analysis. All breast tumours studied were found to express CYP1B1, and not CYP1A1 or CYP1A2. Moreover, CYP1B1 was identified in a number of kidney tumours but not in corresponding normal kidney, indicating that CYP1B1 may be a tumour-specific form of CYP, RT-PCR, in combination with restriction digestion and DNA sequencing, was used to identify CYP mRNA species present in several tumour types. Although CYP1A1 mRNA was identified in breast carcinomas, CYP1B1 was found to be the most frequently expressed form of the CYP1 family in this tissue. CYP3A mRNA was also displayed by several breast tumours, and demonstrated by sequencing to be CYP3A5. A similar situation to breast tumours was observed in tumours of the gastro-intestinal and urinary tracts, with CYP1B1 being the most frequently expressed form of the CYP1 family, and only a small number of samples displaying evidence of CYP1A mRNA. The effects of the expression of xenobiotic metabolising enzymes in tumours may be complex, and depend upon the relative amounts of active protein present, but it is likely that they will exert an influence on both the development of carcinogenesis and the anti-cancer drug resistance of tumours.

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37

Semple, Kirk Taylor. "The biodegradation of phenols by a eukaryotic alga." Thesis, University of Newcastle Upon Tyne, 1994. http://hdl.handle.net/10443/374.

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Axenic cultures of Chiamydomonas ulvaensis [CCAP 11/58], Scenedesmus brasiliensis [CCAP 276/1 B] and Ochromonas danica [0CAP933/28] were screened for their ability to grow on and remove phenol from their incubation media. Neither C. ulvaensis nor S. brasiliensis removed the phenol substrate as rapidly as 0. danica which is a nutritionally versatile chrysophyte. 0. danica was found to grow on phenol and p-cresol as the sole C-source at concentrations up to 4mM in cultures grown in both photoheterotrophic and heterotrophic conditions. The alga would not grow on cresols or xylenols unless phenol was present. Oxygen uptake and turnover studies confirmed that the enzymes involved in phenolic catabolism were inducible and that the organism showed a decrease in activity resulting from the position and number of the methyl substituents on the aromatic ring. [U- 14C]Phenol was completely mineralised with some 65% of the 14C-label appearing as 14CO2, approximately 12% remaining in the aqueous medium and the rest accounted for in the biomass. Analysis of the biomass showed that 14C-label had been incorporated into the protein, nucleic acid and lipid fractions; phenol carbon is thus unequivocally assimilated by the alga. Phenol-grown cultures of 0. danica converted phenol to catechol which was further metabolised by the meta cleavage pathway. 2-Hydroxymuconic semialdehyde and pyruvate, characteristic products of meta cleavage, were found in incubations of catechol with cell-free extracts of phenol-grown cells together with the appropriate enzyme activities. This is , as far as I am aware, the first definitive identification of the meta cleavage pathway for aromatic ring degradation in a eukaryotic microorganism.

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38

Buckberry, Lorraine Dawn. "The biochemistry of mammalian C-S lyases." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.276184.

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Armstrong, Martin John. "The genetic basis of impaired CYP2D6 activity and its relationship to disease susceptibility." Thesis, University of Newcastle Upon Tyne, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357643.

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Todd, Sarah Jane. "The toxicity of xenobiotics to, and their biotransformation by, green microalgae." Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246689.

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Partridge, Toby. "Cloning and expression of a herbicide metabolising cytochrome P450 in plants." Thesis, University of Sheffield, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.264637.

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Kataropoulou, Margarita. "The role of collagen-based substrates in maintainning hepatocyte phenotype in primary culture." Thesis, University of Strathclyde, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275190.

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Altuntas, Tunca Gul. "The in vitro metabolism of isomeric aromatic diazines and some related compounds." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321540.

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Clarke, Stephen Edward. "Characterisation of housefly cytochrome P-450." Thesis, University of Surrey, 1989. http://epubs.surrey.ac.uk/847312/.

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The cytochrome P-450 dependent monooxygenase activity in a 'wild type' susceptible strain of housefly was studied. Catalytic activities were identified that demonstrated that the housefly cytochrome P-450 was capable of similar catalytic functions as those described for higher animals. Although several specific activities were lower than in mammalian species, benzphetamine N-demethylation was comparable and there was higher constitutive activity toward lauric acid than is observed in rat hepatic microsomes. The inducing agent phenobarbital increased both total cytochrome P-450 content and the benzphetamine N-demethylase specific activity. The high constitutive activity for fatty acids was induced by the hypolipidaemic drug clofibrate, specifically inducing the w-hydroxylase activity. The substrate specificity toward lauric acid extended equally to myristic and palmitic acid. Housefly microsomal cytochrome P-450 also metabolised the unsaturated fatty acid, arachidonic acid, the w-hydroxy-lation again inducible by clofibrate pretreatment. The w-hydroxylation of these fatty acids appeared to be a well-coupled reaction, a property that also appeared to be exhibited by the rat hepatic w-hydroxylase. The housefly fatty acid hydroxylation showed certain similarities to that in the rat, both in the specificity for w-hydroxylation and in the result of induction by clofibrate. Structural comparison to cytochrome P-450IVA1, IIB1 and IA1 was made by Western blot analysis with polyclonal antibodies raised to these rat hepatic isoenzymes. Housefly cytochrome P-450 shared few, if any, common epitopes with these rat isoenzymes, nor did these antibodies inhibit housefly cytochrome P-450 dependent monooxygenase activity. Cytochrome P-450 from clofibrate-pretreated housefly microsomes was partially purified by affinity chromatography. The cytochrome P-450 had a specific content of 5. 7nmol.mg-1 and a monomeric molecular weight of 52,000 daltons and a reduced carbon monoxide difference spectrum absorbance maxima at 448nm. In a reconstituted system, this preparation exhibited activity toward lauric acid and to a lesser extent arachidonic acid in each case w-hydroxylated products predominated. This is the first example of a purification of an insect cytochrome P-450 multiple form with a defined product reaction.

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45

Waller, Alan Richard. "Glutathione conjugation in non-human primates." Thesis, University of Surrey, 1985. http://epubs.surrey.ac.uk/848541/.

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The scientific literature indicates that the biotransformation of xenobiotics in man is more similar to that observed in the non-human primate than to other laboratory animal species. The main objective of the current investigation was to compare the ability of 3 species of non-human primate, the rhesus monkey (Macaca mulatta), the cynomolgus monkey (Macaca fascicularis) and the baboon (Papio species), to conjugate xenobiotics with glutathione since such information is lacking in the literature. The metabolism and pharmacokinetics of ethacrynic acid, a diuretic known to be extensively metabolised by glutathione conjugation in several other animal species, was studied in the non-human primates. The results indicate that the overall capacity for glutathione conjugation in the non-human primate is large, and demonstrate that various organs and tissues can simultaneously contribute to the detoxication and elimination of various xenobiotics by this pathway. In common with other laboratory animal species, the non-human primate excreted the major proportion of radioactivity, following administration of [14]C-ethacrynic acid, in the bile. The radioactivity in the bile was mainly associated with metabolites which had resulted from the initial conjugation of ethacrynic acid with glutathione, and the subsequent metabolism of this conjugate via the mercapturic acid pathway. There were notable species differences, between the non-human primates and other laboratory animals, in the proportions of the various metabolites which were excreted in the bile. Although the concentrations of glutathione in the various tissues of the non-human primate were similar to those reported for other mammals, species differences occurred in the rates of glutathione conjugation and the subsequent metabolism of the glutathione conjugate. A significant finding concerned the extent to which various aB-unsaturated xenobiotics were conjugated with glutathione. There were marked species differences between the non-human primate and the rat in this respect. The rhesus monkey, cynomolgus monkey and the baboon are similar as regards ethacrynic acid metabolism, tissue glutathione concentrations, tissue glutathione S-transferase activities, and the specific activities of the glutathione S-transferase isoenzymes. The rhesus monkey more closely resembles man in these respects, but both other species of non-human primate would appear to be suitable for use in metabolism and toxicological studies of compounds likely to be conjugated with glutathione.

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Graham, M. J. "The metabolism of xenobiotics in skin." Thesis, University of Newcastle Upon Tyne, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370158.

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Arend, Markus [Verfasser]. "Bestimmung halogenierter Xenobiotika in Fischen des Nord-Pazifik / Markus Arend." Ulm : Universität Ulm. Fakultät für Naturwissenschaften, 2003. http://d-nb.info/1015354432/34.

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Weiß, Michael [Verfasser]. "Bacterial degradation pathways for xenobiotic and natural organosulfonates / Michael Weiß." Konstanz : Bibliothek der Universität Konstanz, 2015. http://d-nb.info/1110771665/34.

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49

Raheja, Venetia S. Dinakarpandian Deendayal. "Tandem machine learning for identification of xenobiotic-responsive target genes." Diss., UMK access, 2006.

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Thesis (M.S.)--School of Computing and Engineering. University of Missouri--Kansas City, 2006.
"A thesis in computer science." Typescript. Advisor: Deendayal Dinakarpandian. Vita. Title from "catalog record" of the print edition Description based on contents viewed Nov. 9, 2007. Includes bibliographical references (leaves 50-53). Online version of the print edition.

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McLellan, Roman A. "Interindividual differences in xenobiotic-metabolising enzymes : the human genetic factor /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-3924-1/.

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