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1
Cockburn, Elinor M. "The relevance of prostanoid metabolism in the development of drug-induced nephrotoxicity." Thesis, University of Aberdeen, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.481095.
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The enzymes prostaglandin synthetase (PGS) and lipoxygenase can cooxidise a variety of xenobiotics to reactive intermediates during the metabolism of arachidonic acid (AA). PGS exhibited a gradient of activity within the kidney which was greatest in the papilla and least in the cortex. Rabbit and rat renal microsomes metabolised the model compound, tetramethylphenylenediamine (TMPD), in the presence of AA by pathways which were predominantly PGS and lipoxygenase-dependent, respectively. Therefore, both enxymes may play a role in the development of site-specific nephrotoxicity within the kidney. The model papillotoxin 2-bromoethanamine (2-BEA) which exhibits target selective toxicity for the renal papilla, was found to be significantly more toxic to medullary interstitial cells than to proximal tubule cells in culture. Toxicity was enhanced significantly by AA whereas inhibitors of cyclooxygenase (indomethacin, aspirin), prostaglandin hydroperoxidase (propylthiouracyl) and lipoxygenase (nordihydrogauaretic acid) all significantly decreased 2-BEA toxicity. This suggests that toxicity is mediated either by the hydroperoxidase component of PGS or by lipoxygenase. Thromboxane A2 (TxA2) is thought to play a pivotal role in cyclosporin A (CsA) induced nephrotoxicity. Administration of a thromboxane synthetase inhibitor (TSI) normalised TxB2 excretion but only partially protected against other factors involved. However, treatment with angiotensin converting enzyme inhibitor either alone or in combination with TSI did not affect CsA nephrotoxicity. Tubular toxicity, manifest as N-acetyl-β-D-glucosaminidase (NAG) enzymuria, glycosuria, vacuolation, calcification and chronic tubule damage, may contribute to the CsA-induced reduction in renal function. In addition to protecting against CsA-induced nephrotoxicity, the administration of TSI to CsA-treated rats also partially reversed pre-existing renal damage.
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Ferreira, Nuno Gonçalo de Carvalho. "The effects of xenobiotics in biomarkers of porcellionides pruinosus." Master's thesis, Universidade de Aveiro, 2009. http://hdl.handle.net/10773/868.
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Mestrado em Toxicologia e EcotoxicologiaA enorme quantidade de contaminantes quer produzidos pelo Homem (p.e. PHAs, pesticidas, organofosfatos, organocloretos, PBDEs), quer presentes na natureza (p.e. metais) tem um efeito significativamente adverso nos organimos encontrados no meio ambiente. Nos últimos anos, vários biomarcadores têm sido usados na avaliação do efeito de contaminantes no meio ambiente, contudo quase nenhuma informação se centrou no uso desta ferramenta em organismos detritívoros como os isópodes. As reservas energéticas (açucares, lipidos e proteínas) são essenciais para os requisitos de manutenção, crescimento e reprodução de qualquer organismo. As reservas energéticas juntamente com os parâmetros actividade dos sistema de transporte de electrões (STE) e alocação de energia celular (AEC) podem fornecer-nos informação sobre a condição dos organismos quando afectados por contaminantes. Organismos de solo, com o isópode Porcellionides pruinosus, são essenciais para o bom funcionamento dos ecossistemas. Como macrodecompositores, alimentando-se principalmente de matéria vegetal morta, têm um papel importante na cadeia detritívora, através da fragmentação do húmus e pela estimulação e/ou ingestão de fungos e bactérias. São, por isso, organismos importantes na reciclagem de nutrientes. O uso destas espécies chave, juntamente com biomarcadores e conteúdos energéticos poderá ser uma boa ferramenta na avaliação de risco ambiental (ARA). Neste estudo foi avaliado o efeito dos contaminantes zinco e diazinão fornecido por exposição a comida contaminada no isópode Porcellionides pruinosus (Brandt 1833). O estudo baseou-se principalmente no padrão observado nos biomarcadores e nas reservas energéticas para dois tempos de exposição e duas concentrações, já posteriormente descritas como provocando nenhum efeito ou pouco efeito.(5.5 mg zinco/g folha seca, 9.5 mg zinco/g folha seca e de 17.5 μg diazinão/g folha seca, 175 μg diazinão/g folha seca, respectivamente). Para os biomarcadores o tempo de exposição foi de 96h e 7 dias e para as reservas energéticas foi de 7 dias e 14 dias. Os biomarcadores testados foram a acetilcolinesterase (ACHE), lactato desidrogenase (LDH), glutationa S-transferase (GST), glutationa peroxidase (GPx), catalase (CAT) e peroxidação lipídica (LPO). As reservas e conteúdos energéticos medidos foram açúcares, lipidos, proteínas, STE e AEC. Para a exposição a zinco, os biomarcadores GST, CAT e LPO parecem corresponder aos resultados obtidos em outros trabalhos. As reservas energéticas afectadas com uma diminuição significativa foram os açúcares, apresentando também um decréscimo nos valores de ETS e CEA. A exposição a diazinão apresentou diferenças significativas apenas para a ACHE, não apresentado nenhum dos outros biomarcadores alterações de padrões na sua actividade, excepto a GPx para um tempo de exposição de 14 dias. Os lipidos e açúcares foram afectados pela exposição a diazinão e verificou-se também uma diminuição na AEC. ABSTRACT: The enormous amount of contaminants produced by man (i.e. PAHs, pesticides, organophosphates, organochlorides, PBDEs), or that can be found in nature (i.e. metals) has a significant adverse effect on organisms present in the environment. In recent years the biomarkers have been used to evaluate the effects of these contaminants in the environment, but few data has been focused on this assessment tool using detritivorous key-organisms like isopods. Energy reserves (carbohydrates, lipids and proteins) are important for the maintenance, growth and reproduction requirements of any organism. Energy reserves along with the electron transport system activity (ETS) and with the cellular energy allocation (CEA) can give us information about the organisms “status” when affected by the contaminants. Soil key-dwelling organisms like the isopod Porcellionides pruinosus, are essential to the ecosystems’ functions. As macrodecomposers (feeding mainly on decaying plant material) they play an important role in the detritus food chain, through litter fragmentation and stimulating and/or ingesting fungi and bacteria that are important in the cycling of nutrients. The use of these key species along with biomarkers and energy budgets can be a good environmental risk assessment (ERA) endpoint In this work the effects of two environmental contaminants (zinc and diazinon) through food exposure were studied using the isopod Porcellionides pruinosus (Brandt 1833). The study is mainly focused on the effect patterns observed for the biomarkers and energy reserves for two time exposure and two concentrations presented as NOEC and LOEC on previous studies(5.5 μg zinc/g dry leaf, 9.5 μg zinc/g dry leaf and 17.5μg diazinon/g dry leaf, 175μg diazinon/g dry leaf respectively). For biomarkers the exposure time was 96h and 7-days, as for the energy reserves was 7-days and 14-days. The biomarkers tested were acetylcholinesterase (AChE), lactate dehydrogenase (LDH), glutathione S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and lipid peroxidation (LPO). The energy reserves and budget tested were: carbohydrates, lipids, proteins, electrons transport system activity (ETS) and cellular energy allocation (CEA). For zinc exposure the biomarkers GST, CAT and LPO seem to correlate with results obtained for other works. The energy reserves affected were the cabohydrates with significant decrease in their content along with a decrease in both ETS and CEA. The diazinon exposure showed only significative results for AChE, with no changes in all the other biomarkers activity, except the GPx for a 14-day exposure. The energy reserves were affect by a decrease in the carbohydrate and lipid content along with a decrease in the CEA.
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Almeida, Ana Rita Marques. "Combined effects of ultraviolet radiation and xenobiotics on zebrafish." Master's thesis, Universidade de Aveiro, 2013. http://hdl.handle.net/10773/12624.
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Mestrado em Biologia Aplicada - Microbiologia Clínica e AmbientalNowadays, climate changes are an imperative problem and multiple measurements made in the last years showed an increase of all wavelengths of solar radiance, specially the Ultraviolet radiation. In their natural environment organisms are not only affected by biotic and environmental factors, but also by abiotic factors such as xenobiotics. Besides, these both stressors can interact with each other being their combined effect unpredictable (producing additive, synergistic or antagonistic effect). This work aims to studying the combined effect of UV radiation and three xenobiotics: triclosan, potassium dichromate and prochloraz on zebrafish embryos (Danio rerio). Effects were assessed at two levels: i) effects on embryos mortality and ii) effects in the natural bacterial communities of zebrafish embryos. The organisms were exposed to concentrations of each chemical combined with several UV doses. Embryo’ mortality, were observed daily for 96 hours post fertilization (hpf) and natural bacterial communities’ evaluation was performed at 48 hpf. Results showed that different combined effect may occur compromising organism’s survival. Combined exposure of UV radiation with TCS revealed a synergism pattern when the UV radiation is the dominant stressor while PD and PCZ revealed antagonism at low dose levels or when the UV radiation is dominant in the mixture. Zebrafish natural bacterial communities were also affected by UV radiation and chemicals with the change of their structure; however, conclusions about interactive effects were difficult to be drawn because effects were not always translated into changes in the diversity indexes.
Hoje em dia, as alterações climáticas são um problema imperativo e múltiplas medições feitas nos últimos anos mostram um aumento de toda a radiação solar, especialmente a radiação Ultravioleta que chega á superfície da terra afetando todos os organismos expostos. No seu ambiente natural, os organismos não estão apenas sujeitos a fatores bióticos, mas também a fatores ambientais e abióticos como por exemplo os xenobióticos. Além disso, ambos os stressores podem interagir uns com os outros produzindo efeitos imprevisíveis nos organismos (efeitos sinergísticos ou antagonísticos). O presente trabalho tem como objetivo a avaliação dos efeitos combinados da radiação UV e três xenobioticos (triclosan, dicromato de potássio e procloraz) em embriões de peixe zebra (Danio rerio). A avaliação foi feita a dois níveis: i) efeitos na mortalidade de embriões e ii) efeitos a nível das comunidades bacterianas naturais dos embriões. Os organismos foram expostos a várias concentrações de cada químico, combinadas com várias doses de UV. A mortalidade foi registada diariamente durante 96 horas e as comunidades bacterianas naturais foram avaliadas às 48 horas pós fertilização (hpf). Os resultados mostram que diferentes efeitos combinados foram observados, alterando a ecotoxicidade esperada. A exposição combinada da radiação UV com o TCS revelou um patrão sinergístico quando a radiação UV é o stressor dominante, enquanto que, na combinação UV com PD e PCZ observou-se antagonismo a doses baixas ou quando a radiação UV era dominante na mistura. As comunidades bacterianas naturais do peixe zebra também foram afetadas pela radiação UV e químicos, com alterações na sua estrutura. No entanto, foi difícil tirar conclusões relativamente a possíveis interações entre stressors visto que os efeitos observados nem sempre se traduziam em variações no índice de diversidade.
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Kumar, Anila. "A study of the effects of the aminoglycoside antibiotics on a human renal cell line." Thesis, University of Sunderland, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302476.
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Bridges, Christine M. "The effects of a chemical stressor on amphibian larvae : individual, population, and species level responses /." free to MU campus, to others for purchase, 1999. http://wwwlib.umi.com/cr/mo/fullcit?p9946247.
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Hoyle, Vivienne Rosalind. "NMR studies on the biochemical effects of cytochrome P450 inducers and aldose reductase inhibitors." Thesis, Birkbeck (University of London), 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296524.
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Shabir, Shazia. "Indirect effects of cytomegalovirus in kidney transplantation." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7910/.
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Cytomegalovirus (CMV) infection is the most frequent and significant opportunistic infection in kidney transplant recipients. It is associated with direct (CMV disease) and indirect (rejection, poor graft survival) effects with resultant increases in morbidity and mortality. The mechanisms responsible for the indirect effects of CMV infection remain unclear. In this thesis, the indirect effects of cytomegalovirus infection in kidney transplantation are studied. Firstly, the mechanism of CMV infection is investigated. Secondly, the mechanism of CMV associated kidney transplant damage is explored. Thirdly, an assessment for the role of CMV in causing immunosenescence within the kidney transplantation cohort is undertaken. This thesis provides previously undescribed and direct evidence of immune hypo- responsiveness to latent CMV. I have shown CD4⁺CD27⁻CD28^null cells are pathognomonic of prior CMV exposure and have a role in glomerular endothelial cell damage, an effect which may be mediated by NKG2D. Higher CD4⁺CD27⁻CD28^null cell counts at 12 months post-transplantation predict a steeper decline in kidney allograft function thereafter. I provide novel insight into the ‘indirect’ effect of CMV in the pathogenesis of CD8⁺CD28^null cells. My study is the first to demonstrate a temporal association between elevated CD8⁺CD28^null cell frequencies and subsequent development of clinically relevant episodes of infection. The findings from this thesis set the scene for future interventional research and therapeutic strategies.
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Danturti, Sreedevi. "Effects of Adiponectin in Heart and Kidney Transplants." Cleveland State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=csu1483726662977129.
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Eyambe, George Sona. "Cellular Biomarkers for Measuring Toxicity of Xenobiotics: Effects of PCBs on Earthworm Lumbricus Terrestris Coelomocytes." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc332716/.
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The research presented herein provides information on coelomocyte (leukocyte) collection, function and immunotoxicity from polychlorinated biphenyls (PCB) in the earthworm Lumbricus terrestris. Research was undertaken as part of an overall goal to develop a well-documented and scientifically valid non-mammalian surrogate immunoassay with the earthworm Lumbricus terrestris to assess immunotoxic potential of xenobiotics. The principal objectives were to: (1) Develop an extrusion model for analyzing immunotoxicity of xenobiotics; (2) determine if coelomocytes can be collected repeatedly without obvious harm to the earthworm or change in immune response of the coelomocytes harvested and (3) validate the response sensitivity profiles of a panel of biomarkers {differential and total cell counts, erythrocyte rosette (ER) and secretory rosette (SR) formation with, and phagocytosis of antigenic rabbit red blood cells} in earthworms after acute exposure to a known mammalian and L. terrestris immunotoxin, the PCB Aroclor 1254.
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Jing, Yu, and n/a. "The acute effects of lithium on the rat kidney." University of Otago. Department of Physiology, 2008. http://adt.otago.ac.nz./public/adt-NZDU20080930.145652.
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The aim of the experiments reported in the present work was: first, to generate a rat model of lithium-induced nephrogenic diabetes insipidus (NDI), and, second, to use this to test the hypothesis that the effects of lithium were far more reaching than merely the inhibition of vasopressin induced translocation and synthesis of the water channel protein AQP2. Specifically, the effect of lithium on the abundance and distribution of the other water channel proteins, AQP1, AQP3 and AQP4 was investigated. It was found that AQP3 protein abundance was significantly reduced in the renal medulla while AQP4 was not affected. In addition, it was further hypothesized that, given the known effects of lithium on the urea transporter UT-A1 and on sodium channels and transporters, the renal medullary osmotic gradient would be dissipated by lithium. This was examined indirectly by determining the amounts of organic osmolytes in the renal medulla of rats with lithium-induced NDI. Myo-inositol was found to be 85 � 9 mmol kg⁻1 protein in the NDI rats, a reduction of 38% compared with control values, sotbitol fell from 35� 9 mmol kg⁻� in the control rats to 2.5 � 0.5 mmol kg⁻�, and glycerophosphorylcholine levels in the experimental animals were 91 � 18 mmol kg⁻� protein compared with 372 � 72 mmol kg⁻� in the controls. In addition, betaine decreased to 38 � 2 mmol kg⁻� protein from 69 � 10 mmol kg⁻� protein in the control. The urea content of the medulla was found to have fallen from 2868 � 558 mmol kg⁻� protein to 480 � 105 mmol kg⁻� protein. These data indicated that indeed the medullary osmotic gradient, the driving force for AVP-dependent fluid reabsorption in the kidney was greatly reduced during lithium-induced NDI.
Thirdly, it was proposed that the sodium-channel blocker, amiloride, by acting to prevent lithium entry into the cells of the collecting duct, should ameliorate or abolish the adverse effects of lithium on the kidney. Treatment of rats with established NDI, with amiloride, reversed to a large extent the reduction in aquaporin protein expression and re-established the medullary osmotic gradient, as assessed by the ability of treated rats to concentrate their urine, and by the rise in amounts of medullary osmolytes. Administration of 0.5 mmol l⁻� amiloride to lithium-treated rats led to medullary AQP2 and AQP3 protein abundance increasing by 82% � 16% and 110% � 4% of the control level respectively. The content of urea in the medulla also increased to 2474 � 557 mmol kg⁻� protein.
Finally, since in humans it is known that the chronic effect of lithium on the kidney is to cause cortical fibrosis and renal failure, microarray studies were commenced to look for evidence of early changes in gene activity in response to lithium-administration. The results showed that 77 genes were either up- or down-regulated, in particular, genes that are involved in the apoptosis pathway.
In the light of these results it is plausible to suggest that the acute renal effects of lithium to induce NDI can be effectively mitigated, and reversed, by administration of amiloride. Whether this can serve to offset the chronic effects of lithium on the kidney awaits further investigation.
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Polley, Joanne Sarah. "Renal effects of angiotensin, and their modulation by local factors." Thesis, University of Hertfordshire, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296545.
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Furuland, Hans. "Effects of Hemoglobin Normalization with Epoetin in Chronic Kidney Disease." Doctoral thesis, Uppsala University, Department of Medical Sciences, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5816.
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Anemia is common in patients with chronic kidney disease (CDK), contributes to reduced Quality of Life (QoL) and is associated with cardiovascular disease, morbidity and mortality. Epoetin raises hemoglobin (Hb) and increases QoL and physical exercise capacity. Because of concerns about safety and economics, current anemia treatment with epoetin aims to achieve subnormal Hb (110-120 g/l). Normalization of Hb may be of additional benefit regarding QoL and cardiovascular effects. The present study examines the effects of Hb normalization with epoetin on safety variables, QoL, graft function after kidney transplantation, dialysis adequacy, hemorheology, hemodynamics and cardiac autonomic function in CKD patients.
In a randomized, multicenter study comprising 416 pre-dialysis and dialysis patients no difference was observed between patients treated to a normal or a subnormal Hb level on mortality, thrombovascular events, serious adverse events, vascular access thrombosis and residual renal function. QoL was enhanced in a subgroup of hemodialysis patients. Pretransplant epoetin treatment directed toward normal Hb levels did not result in worse graft function during 6 postoperative months. Dialysis adequacy was reduced in a subgroup of hemodialysis patients after normalization of Hb. The blood flow properties of pre-dialysis patients were altered. The hemorheological investigation demonstrated that Hb normalization caused a parallel increase in hematocrit and blood viscosity without other hemorheological changes. While the total peripheral resistance index increased, the cardiac index (CI) decreased. In a separate study cardiac autonomic function, measured by heart rate variability, was decreased in pre-dialysis patients. It was improved, but not fully normalized, by Hb normalization.
On the basis of this study, Hb normalization with epoetin appears to be safe and increases QoL in hemodialysis patients though may result in lower dialysis adequacy and increased blood pressure. A reduction in CI and improved cardiac autonomic function indicate a positive effect on cardiovascular function.
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Treister, Alison Diane. "Effects of Lithium Treatment on Primary Cillia of Mouse Kidney." Thesis, The University of Arizona, 2013. http://hdl.handle.net/10150/297774.
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Treatment with lithium has been shown to have adverse effects on the kidney, but the mechanism has yet to be fully elucidated. In this study, kidney sections of four cohorts of mice were subjected to immunofluorescent labeling in order to determine the effects of lithium on primary cilia. It was found that lithium had a lengthening effect on primary cilia in the inner medulla, outer medulla, and cortex regions of the kidney. It is thought that the effects of longer cilia may include a greater proportion of proteins in the primary cilia. This could lead to alterations in cell signaling in the kidney. Ultimately, lengthening of primary cilia may be responsible for modification of the principal cell and intercalated cell composition following lithium treatment.
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Palmen, Nicole Gertrudis Maria. "Biological effects in human erythrocytes in vitro exposed to xenobiotics influences by metabolizing systems from rat liver /." Maastricht : Maastricht : Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1995. http://arno.unimaas.nl/show.cgi?fid=8338.
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Jolin-Rodrigue, Gabriel. "Effects of Imidacloprid in the Development of Non-Alcoholic Fatty Liver Disease and the Effects of Exercise Training." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/38900.
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The non-alcoholic fatty liver disease (NAFLD) is the most common liver pathology in developed countries with an estimated prevalence of 20 to 30% in the American population. A typically benign and asymptomatic pathology, NAFLD is characterized by hepatic steatosis and abnormal levels of hepatic enzymes stemming from an increase in circulating free fatty acids originating from white adipose tissue lipolysis, an increased de novo lipogenesis, reduced fatty acid oxidation and decreased hepatic triglycerides secretion, all within an insulin resistance context. NAFLD has the potential to progress to the non-alcoholic steatohepatitis (NASH), a condition marked by inflammation, advanced oxidative stress and fibrosis. NASH is expected to be the leading cause of liver transplant by 2020 due to its complications (i.e.: cirrhosis, hepatocellular carcinoma and liver failure). Various xenobiotics such as pesticides have been shown to promote the apparition and development of NAFLD. Of interest to this study is the neonicotinoid imidacloprid, more contemporarily known for its suspected role in the colony collapse disorder of various anthophilae species. Imidacloprid has been shown to induce hepatic oxidative stress in rats, a significant factor in the development of NAFLD and its progression to NASH. Lifestyle modifications, namely physical exercise, is a current treatment which has been proven beneficial to prevent and treat NAFLD by reducing hepatic steatosis, oxidative stress and improving insulin sensitivity. The role of any neonicotinoid on the development of NAFLD has yet to be examine and few have looked at the role of exercise in the treatment of NAFLD brought about by pesticide contamination.
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Chiarappa, Frank E. "The Effects of Exogenous Sry1 and Sry3 on the Rat Kidney." University of Akron / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=akron1269889467.
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Koufaki, Pelagia. "The effects of erythropoietin therapy and exercise rehabilitation on physiological and functional capacity of patients with end stage renal disease." Thesis, Manchester Metropolitan University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364706.
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Kalin, Cigdem. "Effects Of Acrylamide And Resveratrol On Rabbit Liver And Kidney Antioxidant Enzymes." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/3/12611315/index.pdf.
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Resveratrol is one of the promising naturally occurring polyphenolic compound found in red wine having antioxidant and anti-carcinogenic properties. However, in vivo studies investigating the effects of resveratrol on antioxidant enzymes are limited. In the present study, we investigated, for the first time, the influence of resveratrol on liver and kidney antioxidant enzymes and oxidative stress markers in acrylamide treated and control rabbits.
New Zealand male rabbits were treated with acrylamide and resveratrol, separately in two different doses and conditions. Their combined effects were also investigated. While, acrylamide treatment significantly decreased the glutathione peroxidase (GPx) activity in liver (1.24-fold), it was significantly increased (1.20 &ndash1.40-fold) by combined effect of resveratrol and acrylamide in liver and kidney. Furthermore, alone resveratrol administration increased (~1.37 &ndash
fold) GPx activity in kidney. Although, glutathione reductase (GR) was found to be significantly increased (~1.30-fold) in two different dose of resveratrol treated rabbit liver, it was not changed in acrylamide and their combined treatments. Despite, glutathione (GSH) content was decreased around 1.6 fold as a result of acrylamide treatment in rabbit liver and kidney cytosols, GSH level was returned to normal levels by resveratrol tretment in rabbit liver and kidney. Furthermore, acrylamide treatment significantly increased the SDH activity in blood serum (1.68-fold) and in liver (1.27-fold) with respect to control. On the other hand, resveratrol treatment brought this activity nearly normal level in acrylamide treated rabbits.. Besides, sorbitol deydrogenase (SDH) was found to be decreased (3.13-fold) significantly in rabbit liver cytosol as a result of single dose of 100 mg/kg b.w. resveratrol treatment. Moreover, catalase activity and MDA level were not affected from either resveratrol or acrylamide and with their combination effect in investigated rabbit organs. An important liver damage marker enzyme other than ALT and AST, SDH was characterized in terms of substrate, cofactor and enzyme concentration in rabbits which have been not investigated before and found to be 200 mM, 141 µ
M and 0.5 µ
L, respectively in rabbit liver. Furthermore, the Km value was first calculated in liver of New Zealand rabbits as 55,5 mM. In addition to these, in vitro effects of resveratrol on GST activity was also studied throughout this study. Resveratrol was shown to be a noncompetitive inhibitor for liver cytosolic GST against substrate CDNB with Ki of 175 µ
M. On the other hand, resveratrol was shown to be a competitive inhibitor for liver cytosolic GST against substrate GSH with Ki of 55 µ
M. The results of the present study have demonstrated for the first time that resveratrol induced some of the antioxidant enzyme activities and as well nonenzymatic antioxidants in rabbit liver and kidney. The results of GPx, GR, SDH activities and GSH level have also suggested that resveratrol may have protective effects on acrylamide induced hepatoxicity and renal toxicity. Therefore, it may be a therapeutic approach for the oxidative stress-related diseases such as cancer. However, further in vivo studies are required to clarify the effect of resveratrol on both acrylamide-induced toxicity and bioavailability in the body.
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Gurbanov, Rafig. "The Effects Of Selenium On Stz-induced Diabetic Rat Kidney Plasma Membrane." Master's thesis, METU, 2010. http://etd.lib.metu.edu.tr/upload/12611477/index.pdf.
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The kidney is one of the most affected organs of body from diabetes. Diabetic kidney disease is a complication of diabetes seen in 30-40% of diabetic person.
The aim of this work is to contribute the useful information in the therapy of diabetes. It is very important to know the role of antioxidants at the molecular level during diabetes. The protecting role of antioxidants against lipid peroxidation, the effect of cellular antioxidant enzyme systems, understanding the changes of membrane fluidity, lipid order and protein structure which are resulted from antioxidant treatment, determining the effective therapeutic dose with the help of biochemical methods are very important in order to understand the effect of antioxidants at molecular level.
In this thesis work, the Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) was used in order to study the diabetic kidney disease at
the molecular level, which is encountered as a complication of diabetes. Furthermore, the protecting and possible therapeutic role of selenium in the course of diabetic kidney disease was investigated.
To conclude, the kidney plasma membranes were severely deteriorated due to diabetes with respect to its lipid, protein and carbohydrate structure and content, which were corrected after selenium treatment. The diabetes causes diminishment of whole membrane fluidity, which was normalized with the selenium administration. This is the first study demonstrating the effect of diabetes on kidney plasma membrane and the effect of selenium on stz-induced diabetic kidney plasma membranes using spectroscopic tools. The study revealed serious therapeutic and preventing capacities of selenium on diabetic kidney plasma membranes which needs confirmation of future researches. Furthermore, the dosage of selenium given to diabetics should be investigated in detail and proved with biochemical and clinical data.
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Carvalho, Paulo S. M. "Effects of 2,3,7,8-TCDD in rainbow trout early life stages : evaluation at different levels of biological organization with a focus on visual functions /." free to MU campus, to others for purchase, 2002. http://wwwlib.umi.com/cr/mo/fullcit?p3052161.
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Alfvén, Tobias. "Bone and kidney effects from cadmium exposure : dose effect and dose response relationships /." Stockholm : Karolinska Univ. Press, 2002. http://diss.kib.ki.se/2002/91-7349-341-4.
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Lazzara, Matthew J. "Effects of plasma proteins on the sieving of macromolecular tracers in the kidney." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/38443.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2003.Includes bibliographical references (leaves 191-202).
The ultrafiltration of plasma in the mammalian glomerulus is the first step in the processing of blood by the kidney. Proper functioning of this process is critical to the kidney's ability to effectively eliminate waste and retain desirable substances. The glomerular barrier has long been regarded as both a size and charge selective screen for plasma solutes. The origin of this selectivity is found in the unique three-layered structure of the glomerular capillary wall (GCW), consisting of a fenestrated endothelium, the interdigitating foot processes of the glomerular epithelium, and the shared glomerular basement membrane (GBM). The selectivity properties of the GCW have commonly been probed by measuring the sieving coefficients of a variety of tracers, both proteins and exogenous polymers, across the intact glomerular barrier and across isolated components of the GCW. It was found previously that the sieving coefficients of the tracers Ficoll and Ficoll sulfate across isolated GBM were greatly elevated when BSA was present at physiological levels (Bolton et al. 1998). It was suggested that most of this increase was the result of steric interactions between BSA and the tracers which increased tracer partitioning from the bulk into the GBM. Such an effect, if present, would have important implications for the interpretation of macromolecular sieving studies, both in vivo and in vitro. The goals of this thesis research were to model the effect of an abundant protein on the partitioning of a dissimilar tracer molecule, to incorporate that effect into models for glomerular sieving, and to test the partitioning model by measuring the effect of protein concentration on the partitioning of protein and Ficoll in agarose gels. The theoretical effects of solute size on partition coefficients in straight pores or randomly oriented fiber matrices have been investigated previously for very dilute solutions, where solute-solute interactions are negligible, and also for more concentrated solutions consisting of spherical solutes of uniform size. For concentrated solutions it has been found that steric and other repulsive interactions among solutes increase the partition coefficient above the dilute limit. To extend the results for porous or fibrous media to include concentrated mixtures of solutes with different sizes or shapes, we used an excluded volume approach. In this formulation, which describes steric interactions only, partition coefficients were computed by summing all volumes excluded to a solute molecule by virtue of its finite size, the finite size of other solutes, and the presence of fixed obstacles (pore walls or fibers). For a mixture of two spherical solutes, the addition of any second solute at finite concentration increased the partition coefficient of the first solute. That increase was sensitive to the size of the second solute; for a given volume fraction of the second solute, the smaller its radius, the larger the effect. When the total volume fraction of solutes was fixed, an increase in the amount of a second, smaller solute increased the partition coefficient of the first solute, whereas an increase in the amount of a second, larger solute had the opposite effect. Results were obtained also for oblate or prolate spheroidal solutes and for fibrous media with multiple fiber radii. For constant total fiber volume fraction, an increase in the amount of a second, smaller fiber decreased the partition coefficient of a spherical solute, whereas an increase in the amount of a second, larger fiber had the opposite effect. Overall, the theory suggests that the introduction of heterogeneity, whether as mixtures of solute sizes or mixtures of fiber sizes, may cause partition coefficients to differ markedly from those of uniform systems. Using the excluded volume partitioning model, the theory for the sieving of macromolecular tracers was extended to account for the presence of a second, abundant solute. Using that theory, we returned to the experimental data of Bolton et al. (1998) and attempted to model the effect of protein concentration on Ficoll sieving. The osmotic reduction in filtrate velocity caused by an abundant, mostly retained solute will also tend to elevate the tracer sieving coefficient. The osmotic effect alone explained only about one third of the observed increase in the sieving coefficients of Ficoll and Ficoll sulfate, whereas the effect of BSA on tracer partitioning was sufficient to account for the remainder. At physiological concentrations, predictions for tracer sieving in the presence of BSA were found to be insensitive to the assumed shape of the protein (sphere or prolate spheroid). The effect of plasma proteins on tracer partitioning is expected to influence sieving not only in isolated GBM, but also in intact glomerular capillaries in vivo. To test the predicted effects of solute concentration on the equilibrium partitioning of single macromolecules and macromolecule mixtures, measurements of the equilibrium partition coefficients of BSA and four narrow fractions of Ficoll were made in agarose. Solutions of each test macromolecule were equilibrated with a known volume of gel, final liquid concentrations measured, and partition coefficients calculated by applying a material balance. The partition coefficient of each molecule was measured under dilute conditions and under conditions where BSA was present at concentrated levels. All measurements were made for two different gel solid volume fractions (4 and 6%). As expected, the partition coefficients decreased with increasing gel solid volume fraction and with increasing molecular size. Increasing BSA concentration caused an increase in the partitioning of BSA itself and that of all four sizes of Ficoll. This effect was most significant for the largest molecules. A subset of the measurements repeated at a higher ionic strength demonstrated that electrostatic interactions were unimportant. The experimental results were compared with predictions generated from the excluded volume partitioning theory. Agarose was represented as a randomly oriented array of cylindrical fibers, BSA was modeled as a prolate spheroid, and Ficoll was treated as a sphere. Comparisons of the theoretical predictions with the experimental data produced generally good agreement, indicating that steric interactions among solute molecules and between solute molecules and gel fibers could explain the partitioning behavior.
by Matthew Jordan Lazzara.
Ph.D.
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Kilbride, Hannah Speranza. "Estimating GFR and the effects of AKI on progression of chronic kidney disease." Thesis, University of Kent, 2015. https://kar.kent.ac.uk/53613/.
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Chronic kidney disease (CKD) is a common health problem with a high prevalence in the elderly and is associated with high mortality rates and co-morbidity. CKD guidelines recommend that diagnosis and staging of CKD be based on estimated glomerular filtration rate (eGFR). Estimating GFR requires estimating equations using the variables gender, race and age and body surface area based on serum creatinine levels. The commonly recommended and used equations are the Modification of Diet in Renal Disease (MDRD) study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations but these have not yet been validated in elderly people, who are at significant risk of developing CKD. The numbers of patients with progressive CKD is reportedly low with only a small proportion of patients reaching end-stage renal disease (ESRD). This study set out to find out why there is such a disproportion in the high prevalence of CKD and the low incidence of ESRD patients. Many patients die before they reach ESRD but prevalence studies have shown that mortality rates alone do not account for these numbers. I hypothesised that the methods used to estimate GFR underestimate renal function in elderly people causing an overestimate in CKD prevalence. This study firstly set out to assess the accuracy of the MDRD and CKD-EPI equations in an elderly Caucasian population against measured GFR across a wide range of renal function. The study demonstrated both equations perform fairly accurately in the elderly population with a tendency to slightly over-estimate GFR. This study has validated the use of these estimating equations in an elderly Caucasian population disproving my first hypothesis. If the CKD prevalence data is a fair estimate and only a small proportion progress then the answer may lie in how CKD progresses. There are several known factors that influence CKD progression including GFR and albuminuria category, cause of renal disease and hypertension. Some of these risk factors are modifiable and need to be identified and managed in order to impact on long term outcomes including death, cardiovascular events and disease progression. Acute kidney injury (AKI) is also rising in incidence and is complicated by high mortality rates, increased risk of cardiovascular events and more recently CKD progression. Little is known about the impact of more minor episodes occurring in the community on renal outcome. The second part of this study examined the relationship of multiple episodes of community AKI with CKD progression in a population of patients with CKD stage 3-5 referred to renal services. In this observational study, patterns of CKD progression were assessed and multiple AKI events were recorded. This study demonstrated a clear relation between multiple AKI events and CKD progression however only low eGFR at referral, diabetes and albuminuria were independent risk factors associated with disease progression. During the study it emerged that there were two patterns of CKD progression. In comparison to the more commonly assumed linear decline, the more common pattern was a stepwise progressive pattern characterised by accelerated rates of decline followed by a period of stability. Multiple AKI events were significantly more common in the stepwise progressive group suggesting AKI may have an important role as a promoter of CKD progression. This study suggests that community AKI is a modifiable risk factor that needs identifying at early stages in order to minimise risk of poor outcomes including CKD progression.
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Simboli-Campbell, Maura E. "The role of protein kinase C in vitamin D-mediated effects in kidney." Thesis, University of Ottawa (Canada), 1993. http://hdl.handle.net/10393/6608.
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The role of the calcium/phospholipid-dependent serine/threonine kinase Protein Kinase C (PKC), in the effects of vitamin D on kidney was studied. Madin Darby Bovine Kidney (MDBK) cells, a normal epithelial-like cell line, were found to express the Vitamin D Receptor (VDR) and the vitamin D-dependent calcium binding protein Calbindin D-28K (CaBP D-28K). In MDBK cells, 1,25(OH)$\sb2\rm D\sb3$ increased PKC activity in a time- and dose-dependent manner as measured by two different phosphorylation assays. This activation appeared to result from translocation of PKC from the cytosol to the membrane and was accompanied by an increase in immunoreactive PKC in the membrane. PKC was also activated by short term exposure of MDBK cells to TPA, whereas PKC activity was completely down-regulated by long term exposure to TPA. Down-regulation of PKC activity was accompanied by a loss of immunoreactive PKC. The phorbol ester analogue 4$\alpha$PDD had no effect on PKC activity or amount. Concurrent with activation of PKC 1,25(OH)$\sb2\rm D\sb3$ homologously up-regulated the VDR and increased total immunoreactive CaBP D-28K in MDBK cells. In contrast, down-regulation of PKC activity in TPA treated cells was associated with decreased expression of the VDR and CaBP D-28K. The phorbol ester analogue 4$\alpha$PDD, which had no effect on PKC, did not affect the expression of the VDR or CaBP D-28K. Short term TPA treatment, which activated PKC, increased CaBP D-28K without altering VDR levels. The divergent effects of 1,25(OH)$\sb2\rm D\sb3$ and TPA were associated with differential regulation of PKC isozymes. Treatment of MDBK cells with 1,25(OH)$\sb2\rm D\sb3$ increased membrane association of PKC $\alpha,$ induced nuclear translocation of PKC $\beta$ and had no effect on PKC $\zeta.$ In contrast, long term treatment of MDBK cells with TPA induced down-regulation of PKC $\alpha,$ nuclear translocation of PKC $\beta,$ and decreased PKC $\zeta.$ Nuclear translocation of PKC $\beta$ by 1,25(OH)$\sb2\rm D\sb3$ treatment was accompanied by an increase in phosphorylation of endogenous nuclear proteins. However nuclear translocation of PKC $\beta$ by TPA treatment did not affect phosphorylation of endogenous nuclear proteins. The data have been incorporated into a model based on the hypothesis that the VDR could be a nuclear substrate for PKC $\beta$ and CaBP D-28K could be a cytosolic substrate for PKC $\alpha.$ This model predicts a novel role for PKC-dependent phosphorylations in the renal actions of 1,25(OH)$\sb2\rm D\sb3.$
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Hanzlicek, Andrew S. "The effects of rheum officinale on the progression of feline chronic kidney disease." Thesis, Kansas State University, 2011. http://hdl.handle.net/2097/9265.
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Master of ScienceDepartment of Clinical Sciences
Gregory F. Grauer
Chronic kidney disease (CKD) is a common cause of morbidity and mortality in cats. The purpose of this study was to investigate the effects of Chinese rhubarb (Rheum officinale) supplementation on the progression of feline CKD. Cats with stable IRIS stage II or III CKD and without certain comorbidities were included in the study. Cats were randomly divided into 3 treatment groups and administered Chinese rhubarb extract (Group 1, Rubenal®, Vetoquinol, Forth Worth, TX; 75 mg tablet by mouth every 12 h), benazepril as a positive control (Group 2, 0.5 mg/kg by mouth every 24 h), or both (Group 3). Cats were fed a commercial renal specific diet and enteric phosphate binder as appropriate. Body weight, laboratory data, and blood pressure were recorded every 3 months. Variables between groups at enrollment and within groups over visits were compared with ANOVA and repeated measures ANOVA, respectively. A treatment by visit interaction term was included in all repeated measures models. Significance was set at p ≤ 0.05. Except for body weight there was no significant differences between treatment groups at enrollment. There was no significant change in body weight, hematocrit (Hct), UPC, serum creatinine, or systemic blood pressure over time as compared to baseline within any group. There was no significant difference between groups over time in regards to change in body weight, Hct, UPC, serum creatinine, or systemic blood pressure. The treatment by time interaction was non-significant in all models. Based on easily measured clinical parameters, this study failed to detect a significant difference in cats administered a Chinese rhubarb supplement, benazepril, or both.
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Watson, Joanne Elaine. "The effects of TPA and overexpression of WT1 on the 293 cell line." Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.480893.
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Avades, Tony. "Renal effects of X-ray contrast media in different experimental models." Thesis, University of Surrey, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388979.
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Nyman, Madeleine. "Biomarkers for exposure and for the effects of contamination with polyhalogenated aromatic hydrocarbons in Baltic ringed and grey seals." Helsinki : University of Helsinki, 2000. http://ethesis.helsinki.fi/julkaisut/mat/ekolo/vk/nyman/.
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Heiwe, Susanne. "Experienced physical functioning and effects of resistance training in patients with chronic kidney disease /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-865-3/.
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Saxby, Mark Fraser. "An analysis of the effects and effectiveness of medical and surgical treatments on the kidney." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243308.
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Chan, Wing Lam Winnie. "Effects of body composition on clinical and quality of life outcomes in kidney transplant recipients." Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5581/.
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Sarcopenic obesity is common among kidney transplant recipients. Fluid volume status has not been well-investigated following kidney transplantation. This thesis aimed to explore the effects of body composition, including fat mass, muscle mass and fluid volume status, on post-transplantation morbidity and fatigue. These are potential contributing factors to long-term patient- and graft- survival, as well as quality of life. Firstly, the associations between adiposity with inflammation, hepcidin and haemoglobin levels were investigated. Secondly, the effects of hypervolemia on blood pressure and levels of N-terminal fragment of pro-hormone B-type natriuretic peptide (NT-proBNP) were explored. Thirdly, the role of muscle mass and fat mass on all domains of fatigue were studied. Finally, the mechanistic aetiology of physical fatigue was examined by evaluation of muscle mass, muscular and cardiovascular functions, and fatigue perception. This thesis concluded that while adiposity displays significant independent association with inflammation, its role in determining hepcidin and haemoglobin levels remains uncertain. Reduced muscle mass may be correlated with physical fatigue, but independent contribution of fat mass in fatigue remains undefined. Hypervolemia is associated with raised blood pressure and elevated levels of NT-proBNP. The findings from this thesis set the scene for future interventional research and therapeutic strategies.
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Tran, Lily H., Serena A. Allen, Hannah V. Oakes, Russell W. Brown, and Brooks B. Pond. "Dopaminergic Effects of major Bath Salt Constituents 3, 4-methylenedioxypyrovalerone (MDPV), Mephedrone, and Methylone are Enhanced Following Co-exposure." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/139.
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An unprecedented rise in the availability of new synthetic drugs of abuse has been observed in the recent years. One of the most noted cases is that of a popularized designer drug mixture known as ‘bath salts’. Commonly obtained from various shops and on the internet, “bath salts” often contain the synthetic cathinones 3,4 methylenedioxypyrovalerone (MDPV), mephedrone, and methylone in diverse combinations. Individually, the synthetic cathinones are known to have similar pharmacology to controlled psychostimulants such as cocaine and the amphetamines, increasing the levels of dopamine (DA) in the synaptic cleft. DA is an important neurotransmitter that regulates a variety of behaviors and functions; neurons within the mesolimbic DA pathway (ventral tegmental area to nucleus accumbens) are involved in reward and motivation and are activated by these drugs of abuse. Additionally, psychostimulant-induced increases in DA in the nigrostriatal pathway (substantia nigra to corpus striatum) lead to increases in locomotor behavior. However, the majority of preclinical investigations have only assessed the effects of individual bath salt constituents and have provided little information regarding the possibility of significant drug interactions with the co-exposure of MDPV, mephedrone, and methylone. This study sought to evaluate and compare the effects of individual versus combined MDPV, mephedrone, and methylone on dopamine (DA) levels in discrete brain regions as well as motor stimulant responses in mice. Male adolescent Swiss-Webster mice received intraperitoneal injections of saline, MDPV, mephedrone, methylone (1.0 or 10.0 mg/kg), or the cathinone cocktail (MDPV + mephedrone + methylone at 1.0, 3.3, or 10 mg/kg). The effect of each treatment on DA and DA metabolite levels in mesolimbic and nigrostriatal brain tissue was quantified 15 min after a single exposure utilizing high pressure liquid chromatography with electrochemical detection (HPLC-ECD). Additionally, locomotor activity was recorded in mice after acute (day 1) and chronic intermittent (day 7) dosing. The results demonstrate that MDPV, mephedrone, and methylone produce dose-related increases in the mesolimbic and nigrostriatal DA levels that are significantly enhanced following their co-administration. Additionally, a decrease in locomotor activity on day 1 that was exacerbated by day 7 was noted in mice treated with the cathinone cocktail and was not observed with any of the single agents. The decrease in locomotor activity was accompanied by an increase in stereotypic-like behavior including excessive grooming and even self-mutilation. Our findings demonstrate a significantly enhanced effect of MDPV, mephedrone, and methylone on both DA and its metabolites resulting in significant alterations in locomotor activity. This work provides insight into the potential enhanced risk of the use of these combination synthetic cathinone products.
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Hamel, Owen Sprague. "The dynamics and effects of bacterial kidney disease in Snake River spring Chinook salmon (Oncorhynchus tshawytscha) /." Thesis, Connect to this title online; UW restricted, 2001. http://hdl.handle.net/1773/6364.
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Adang, Edwin Mathias Marie. "Medical technology assessment in surgery costs and effects of dynamic graciloplasty and combined pancreas kidney transplantation /." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 1997. http://arno.unimaas.nl/show.cgi?fid=5901.
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Sandouka, Ashraf. "Carbon monoxide-releasing molecules (CO-RMs) : effects on physiology and ischaemia-reperfusion injury in the kidney." Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445042/.
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Background: Although high concentrations of carbon monoxide (CO) are unquestionably toxic, emerging evidence reveals that CO at low concentrations plays a significant role in vasorelaxation, blockade of apoptotic pathways, suppression of inflammation and protection against ischaemia-reperfusion (I-R) injury. Our group has recently identified a series of compounds (CO-releasing molecules or CO-RMs) which exert important pharmacological activities by carrying and delivering CO to biological systems.;Aims: The present study was designed to evaluate the influence of CO released from CO-RMs on mitochondrial respiration and its consequences on renal haemodynamic, biochemical, and physiological parameters as well as to examine the possible beneficial effects of CO-RMs against I-R injury.;Methods: Parallel experiments were conducted using: 1) the isolated renal cortical rat mitochondria for evaluation of oxygen consumption, hydrogen peroxide production, and lipid peroxidation. 2) the ex vivo isolated perfused rabbit kidney (IPRK) model to measure the physiological and biochemical parameters and mitochondrial respiration for freshly harvested kidneys and kidneys exposed to ischaemic injury, and 3) an in vitro model of renal proximal tubular epithelial (LLC-PKi) cells to assess membrane integrity and metabolic activity.;Results: The major findings of this study indicate that CO modulates mitochondrial respiratory activity in isolated rat mitochondria. In IPRK model, CO reduces tubular reabsorption and increases urine and perfusion flow rate and glomerular filtration rate of freshly isolated kidneys. However, in IPRK model, kidneys flushed with a cold preservation solution supplemented with CO-RMs and stored at 4 C for 24 or 48 hr displayed at reperfusion a significant protective vasodilatory effect, improved renal function and mitochondrial respiration compared to control kidneys flushed with cold solution alone. Additionally, CO released from CO-RMs protects against preservation injury using the in vitro model of LLC-PKi cells. In contrast, in a warm I-R model using the IPRK circuit, CO was only beneficial by increasing the perfusate flow rate at reperfusion.;Conclusion: the results emphasize that CO liberated from CO-RMs has a protective vasodilatory effect, improves renal function and increases mitochondrial respiration after cold ischaemia and reperfusion. These findings suggest that CO-RMs could be used therapeutically in preservation solutions as an efficacious strategy to prevent the injury sustained by organs during cold storage prior to transplantation.
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Lomas, Amy. "The renal effects of nonsteroidal anti-inflammatory drugs (NSAIDS) in dogs with chronic kidney disease (CKD)." Thesis, Kansas State University, 2013. http://hdl.handle.net/2097/20475.
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Master of ScienceDepartment of Clinical Sciences
Gregory F. Grauer
Prostaglandins play many important roles in the kidney including regulation of renal blood flow, glomerular filtration, renin release, and sodium excretion. Upon activation of the renin angiotensin aldosterone system (RAAS), prostaglandin upregulation becomes critical to offset the vasoconstrictive effects of norephinephrine, angiotensin II, and vasopressin. Nonsteroidal anti-inflammatory drugs (NSAIDs) produce both their beneficial and detrimental effects through inhibition of the cyclooxygenase enzyme and subsequent interference with prostaglandin production. Healthy canine kidneys express both COX-1 and COX-2, although basal COX-2 expression in dogs is significantly higher than in other species. Nonsteroidal anti-inflammatory drugs that spare COX-1 have exhibited less gastrointestinal toxicity, but no NSAID has been proven safe for the kidney. The kidney is the organ with the second highest reports of adverse drug events, which is usually manifested as functional changes. However, structural changes including renal papillary necrosis, can occasionally be observed. Dogs with chronic kidney disease could be expected to be at increased risk for NSAID-related adverse drug effects. As nephrons and renal reserve are lost in chronic kidney disease, the canine kidney becomes more dependent on COX-2 for production of prostaglandins. Inasmuch as the prevalence of both CKD and OA increases with age, it is expected that many dogs being treated with NSAIDs for OA will have loss of renal reserve and/or early stage CKD. If administration of an NSAID is required for long term treatment of osteoarthritis, frequent monitoring of blood pressure and renal parameters, as well as hepatic enzymes are recommended.
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Thomas, Mark Edward. "Studies of the pathophysiological effects of fatty acid bearing albumin in models of proteinuric kidney disease." Thesis, University of Leicester, 1997. http://hdl.handle.net/2381/29370.
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Proteinuria may be directly responsible for promoting tubulointerstitial injury. The fatty acids carried on filtered albumin are taken up by the proximal tubule, where they could contribute to tubulointerstitial injury.;The effects of fatty acid-albumin complexes have been studied in Opossum kidney (OK) cells, a proximal tubule cell line, OK cells transported two-thirds of 142C-palmitate-ablumin intracellularly within 16 hours. Less than 1% of 14C-palmitate taken up was isolated as intracellular free fatty acid. Less than 5% of 14 C-palmitate internalised was oxidised to 14CO2. 14C-palmitate-albumin was distributed into phosphatidylcholines, phosphatidylinositols, and triglycerides. 14C-labelled unsaturated fatty acid-albumins (oleate, linoleate and arachidonate) showed preferential incorporation into triglycerides, with lesser incorporation into phospholipids. Fatty acid-albumin uptake produced a marked 10-fold increase in total triglyceride levels. Oil Red O staining of OK cells cultured with oleate-albumin showed a marked increase in intracellular lipid droplets, indicating triglyceride accumulation. Different fatty acids, when taken up by the OK cell, have distinct metabolic fates. Each fatty acid is incorporated into certain specific complex lipids, possibly dependent on the presence or absence of double bonds.;The effects of fatty acid-albumin complexes on OK cell growth were studied. Palmitate-albumin and myristate-albumin markedly inhibited while oleate-albumin stimulated OK cell growth. The growth inhibitory effect of palmitate-albumin occurred in the absence of significant cellular toxicity, and was prevented by the presence of an equimolar concentration of oleate-albumin. Uptake of mainly saturated fatty acid-albumin complexes by the proximal tubule could inhibit its regeneration after injury.;The effects of fatty acid bearing albumin were studied in the protein-overload model of proteinuria.;In conclusion, this work has provided new evidence that the fatty acids carried out on albumin may have important metabolic and pathophysiological effects on the proximal tubule, which could contribute to the progression of proteinuric renal disease.
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Goldstein, D. Jordi. "Effects of selective manipulation of fatty acids in experimental chronic renal disease." Thesis, Boston University, 1993. https://hdl.handle.net/2144/31818.
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Thesis (D.Sc.N.S.)--Boston University, Henry M. Goldman School of Graduate Dentistry, 1993 (Nutritional Sciences).Includes bibliography (leaves 176-187)
This dissertation has been presented in two related studies: A. Fish Oil Reduces Proteinuria and Interstitial Injury but not GIomerulosclerosis in the Milan Nomotensive Rat Rats of the Milan Normotensive strain (MNS) spontaneously develop severe Proteinuria and excessive glomemlar thromboxane (Tx)A2 PrOduction at a young age. These are accompanied by podocyte alterations and progressive focal glomerulosclerosis (FGS) and interstitial fibrosis. Since previous studies showed that pharmacologic... [TRUNCATED]
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Zhang, Zhongsheng. "Effects of electric field on the functions of cell membrane proteins." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002308.
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Nilsson, Sommar Johan. "Prospective and longitudinal human studies of lead and cadmium exposure and the kidney." Doctoral thesis, Umeå universitet, Yrkes- och miljömedicin, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-67832.
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Cadmium and lead accumulate in humans and can have toxic effects. Exposure to cadmium is well known to cause kidney damage. Cadmium binds to metallothioneins, proteins that play a role in cadmium transport. Lead exposure’s main effect is on the central nervous system, but associations with kidney disease have also been found, although it is unknown if the latter is a causal association. The main source of both metals within the non-smoking population is from the diet. This thesis aims to 1) compare the biomarkers lead and cadmium concentration in whole-blood, plasma and urine with regard to their ability to discriminate between individuals with different mean concentrations, and to describe the effect of urinary dilution, 2) estimate the association between end-stage renal disease and blood concentrations of cadmium, lead and mercury, using prospectively collected samples for exposure evaluation, 3) use longitudinal data on kidney function makers to evaluate kidney recovery after a substantial decrease in cadmium exposure, and 4) assess the influence of metallothionein polymorphisms (MT1A rs11076161, MT2A rs10636 and MT2A rs28366003) on cadmium-associated kidney toxicity and recovery due to a reduction in Cd exposure. Repeated sampling of whole-blood, plasma and urine was conducted on 48 occupationally lead-exposed men and 20 individuals under normal environmental lead exposure, for estimation of the day-to-day and between individual-variation. Prospective samples were obtained for 118 cases that later in life developed end-stage renal disease, and 378 matched controls. Erythrocyte cadmium, lead, and mercury concentrations were determined and the risk of developing end-stage renal disease associated with metal concentrations was estimated. For evaluation of kidney recovery after a reduction in cadmium exposure and to test for gene-environment interactions, follow-up data on N-acetyl-β‑d-glucosaminidase, β2‑microglobulin, albumin, and gene polymorphisms were obtained for 412 individuals within the Chinese population and the relation to blood and urinary cadmium was assessed. The concentration of lead in blood was found to be the biomarker with the largest fraction of the total variance attributable to between-individual variation, and was therefore the biomarker with the best ability to discriminate between individuals with different mean concentrations, both for individuals under occupational and normal environmental exposure (91 and 95%, respectively). Adjusting for urinary dilution had a great effect on the fraction of the total variance attributable to between-individual variation among individuals with normal lead exposure but only a minor effect among those who were occupationally exposed. Variance analysis showed that blood concentrations were also the best discriminating biomarker for cadmium. Erythrocyte lead was, in a univariate model, associated with an increased risk of developing end-stage renal disease [odds ratio (OR) = 1.54 for an interquartile range increase, with a 95% confidence interval (CI) = 1.18-2.00], while erythrocyte mercury was negatively associated (OR = 0.75 for an interquartile range increase, with a 95% CI = 0.56-0.99). For erythrocyte cadmium, the OR was 1.15 with a 95% CI of 0.99-1.34. Associations with lead and cadmium were only seen among men. In the study on kidney recovery, the proportion of individuals with albumin level above the 95th percentile decreased between baseline and follow up, but no decrease was found for the tubular markers N-acetyl-β‑d-glucosaminidase and β2-microglobulin. Metallothionein polymorphisms modified cadmium-associated effects on N-acetyl-β‑d-glucosaminidase and β2-microglobulin levels but did not modify cadmium-associated change in any of the kidney function markers between baseline and follow up after a substantial decrease in exposure. Blood concentrations of lead and cadmium are the biomarkers with the best ability to discriminate between individuals with different mean concentrations. Adjustment for urinary dilution has great influence on the fraction of the total variance attributed to between individual variation among urine samples with low lead concentrations, but only a small influence on samples with high lead concentrations. This suggests a difference in excretion. The association between end-stage renal disease and low-level lead exposure, as assessed through prospective erythrocyte samples, gives reason for concern, although further studies are needed to determine causality. A cadmium-associated increase in albumin is reversible after a substantial reduction in exposure, but this is not the case for the observed tubular effects. The tubular kidney effects of cadmium might be modified by the MT1A rs11076161 polymorphism.För att bedöma exponering för kadmium och bly mäts ofta deras koncentrationer i blod eller urin. Dessa studerades i longitudinella data för 48 blyarbetare och 20 individer med normal miljömässig exponering. Blod- och urinprover togs var annan till var tredje månad. Kadmium- och blykoncentrationer mättes sedan i helblod, plasma och urin. Koncentrationer av bly i blod var den biomarkör som hade den största andelen av den totala variationen som kunde förklaras av skillnader mellan individer, och var därför den biomarkör med den bästa förmågan att särskilja på individer med olika medelkoncentration, både för individer med yrkesexponering och normal miljömässig exponering (91 respektive 95% av variansen berodde på vilken individ blodprovet kom ifrån). Justering för urinens utspädning av bly i urin förbättrar oftast urins användbarhet som biomarkör. För bly stämde detta bara hos dem som inte var blyarbetare. Blodkoncentrationer var också den biomarkör med störst andel av den totala variation som kunde förklaras med skillnader mellan individer för kadmium. Kadmium och bly ackumuleras i njure respektive ben och kan ha toxikologiska effekter. Det är välkänt att höga exponeringsnivåer av kadmium orsakar njurskada och även vid lägre exponeringsnivåer har studier funnit samband med markörer för njurfunktion. Exponering för bly påverkar i första hand det centrala nervsystemet. Studier har dock funnit samband mellan koncentrationer av bly i blod och njurens glomerulära filtrationshastighet. Det är oklart både om dessa associationer, vid låga exponeringsnivåer, är viktiga för hälsan och om de verkligen beror på att kadmium och bly orsakar njurskada. För att studera end-stage renal disease användes prospektiva kohorter där personer lämnat blodprov för forskning: Västerbottens interventionsprogram med prover som tagits vid Västerbottens hälsoundersökningar, MONICA-undersökningar i Norr- och Västerbotten, mammografiundersökningarna i Västerbotten och Malmö kost cancer. Sammanlagt ingick över ett hundra tusen individer i dessa kohorter. Med hjälp av det Svenska njurregistret identifierades sedan 118 personer som senare i livet fått end-stage renal disease. Dessa jämfördes med 378 kontroller. För dessa 496 personer tinades blodprovet (närmare bestämt röda blodkroppar) upp och analyserades för kadmium och bly. För att undersöka njurens förmåga till återhämtning studerades tre områden i Kina varav ett tidigare varit kraftigt kadmiumexponerat. Erytrocytkoncentrationer av bly var, utan att ta hänsyn till några andra variabler, associerat med en ökad risk för att utveckla end-stage renal disease (med oddskvoten 1.54 för en interquartile range ökning av erytrocytbly, med ett 95% konfidensintervall 1.18-2.00). Sambanden kvarstod också efter att ha tagit hänsyn till övriga variabler. För erytrocytkadmium var oddskvoten 1.15 med 95% konfidensintervall 0.99-1.34, och sambandet försvagades när hänsyn togs till andra variabler. Associationerna sågs bland män men inte bland kvinnor. Eftersom kadmium vid höga nivåer orsakar njurskada är det också av intresse att studera om påverkan på njuren går över om exponeringen minskas. Totalt följdes 412 individer upp med mätningar av markörer för njurfunktion och kadmiumkoncentrationer i blod och urin. Första undersökningen gjordes 1998, då man just hade slutat äta kadmiumförorenat ris. En andra undersökning gjordes 2006. Andelen individer med avvikande albuminvärde i urin var lägre vid uppföljningen jämfört med vid baslinjen, men ingen minskning sågs för markörer för tubulär förmåga att återta proteiner. Åttioprocent av kadmium i celler är bundet till proteinet metallotheonin, vilket skyddar mot cellskada, men har också en roll i transporten av kadmium från levern till njurarna. En tidigare studie har visat att njurens känslighet för kadmiumexponering var associerad med genetiska skillnader i detta protein. För att studera genetiska associationer studerades de 412 personerna i den kinesiska studien [då också individernas genotyper av metallotheonin-polymorfierna MT1A rs11076161 (G/A), MT2A rs10636 (G/C) och MT2A rs28366003 (A/G) bestämdes]. Genetiken spelade roll för sambandet mellan förmåga att återta proteiner och kadmium men påverkade inte förändring av njurfunktion efter att man slutat äta kadmiumförorenat ris. Kadmium- och blykoncentrationer i blod är de biomarkörer, av koncentrationer i blod, plasma och urin, med den bästa förmågan att skilja på individer med olika medelkoncentrationer. Justering för urinutspädning påverkade andelen av den totala variationen som kunde förklaras av skillnader mellan individer i stor utsträckning för individer med normal miljömässig exponering men inte bland yrkesexponerade, vilket tyder på en skillnad i hur utsöndringen går till. Associationen mellan end-stage renal disease och låg exponering för bly, uppmätta i prospektiva erytrocytprover, ger orsak till oro, men ytterligare studier behövs för att kunna utvärdera om detta är ett kausalt samband. En kadmiumrelaterad skada av den glomerulära filtrationen är reversibel efter en kraftig reducering i exponering, men detta är inte fallet för tubulär skada. De tubulära njureffekterna av kadmiumexponering kan påverkas av metallotheonin-polymorfier.
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Ma, Qiuyue [Verfasser], and Hans-Joachim [Akademischer Betreuer] Anders. "The effects of hyperuricemia on sterile inflammation during chronic kidney disease / Qiuyue Ma ; Betreuer: Hans-Joachim Anders." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/1223369749/34.
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Pile, Taryn. "Anaemia in kidney transplant recipients : effects of recombinant human erythropoietin and the potential role of mycophenolate mofetil." Thesis, Queen Mary, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.576916.
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Background Anaemia is common in patients with functioning kidney transplants. Mycophenolic acid (MPA) is anecdotally associated with anaemia, but the mechanism of action is not proven. The effect of recombinant human erythropoietin (rHuEPO) in this setting is poorly studied. Hypothesis 1) MPA causes decreased erythropoiesis in vitro. 2) rHuEPO treatment attenuates progression of renal failure in Post-Transplant Anaemia (PTA). 3) rHuEPO treatment improves Health Quality of Life (HRQOL) and cardiovascular biomarkers. Methods An in vitro model of erythropoiesis in UT-7 cells (human haemo-Ieukaemic cells responsive to EPO) and murine bone marrow cells was used to study the effects of mycophenolic acid on erythroid cell lines. An open labelled, randomised, controlled trial of the use of rHuEPO in anaemic kidney transplant recipients (KTRs) was performed. The primary end points were renal progression measured by rate of change of estimated Glomerular Filtration Rate (eGFR),; change in Protein: Creatinine Ratio (P: CR) and change in blood pressure (B~). Secondary outcomes were changes in SF-36® Health Quality-of-Life (HRQOL) scores and change in Left Ventricular Mass Index (LVMI). A subgroup of the trial was studied for changes in cardiovascular biomarkers using flow cytometry. Results MPA significantly decreased both the proliferation of UT-7 cells (P < 0.001) and erythropoiesis in murine bone marrow cells (P < 0.0001). This was associated with an increase in caspase-3 activity in UT-7 cells in a dose-dependent manner (P < 0.01). Inhibition was reversed in UT-7 cells and in murine bone marrow by guanosine, but not by caspase inhibitors. The apoptosis induced by MPA was also reversed by guanosine. UT-7 cells treated with MPA showed a decrease IMPDH activity. Epoetin beta (the rHuEPO used) treatment improved haemoglobin concentration resulting in a significant improvement of the Vitality Health Domain scales of the SF-36 QOL in the treatment group (P = 0.02). There was no significant difference in the primary outcomes. There was no difference in LVMI or in cardiovascular biomarkers. Conclusion Mycophenolic acid inhibits proliferation of UT-7 cells and inhibits erythropoiesis in murine bone marrow cells via direct inhibition of IMPDH. These in vitro findings offer an explanation to the clinical association of anaemia and MPA use. The treatment with rHuEPO of PTA was found to be associated with improved HRQOL in certain domains. There were no obvious safety concerns demonstrated. However it did not affect the rate of progression of renal failure. Similarly no effect was seen on biomarkers of cardiovascular morbidity.
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Becker, Bryan A. "The effects of ischemia-reperfusion injury on cytosolic and mitochondrial levels of glutathione in the rat kidney." Virtual Press, 2001. http://liblink.bsu.edu/uhtbin/catkey/1204198.
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This study was done to investigate the effect of ischemia-reperfusion injury on cytosolic and mitochondrial glutathione levels in the rat kidney. Glutathione is the main cellular defense against free radicals that are thought to cause ischemia-reperfusion injury. Right kidneys from anesthetized female Lewis rats (9-12 months old) were exposed to 60 minutes of ischemia followed by 0, 30, or 120 minutes of reperfusion. The kidneys were perfused with isotonic saline, harvested, homogenized, and separated into cytosolic and mitochondrial fractions by differential centrifugation. Reduced (GSH) and oxidized (GSSG) glutathione levels were measured spectrophotometrically. There were significant decreases in both the GSH levels and the % GSH/Total Glutathione in the cytosol and mitochondria of kidneys exposed to ischemia-reperfusion injury when compared to control kidneys. The glutathione levels in either the cytosol or mitochondria did not recover even after 120 minutes of reperfusion. This study demonstrates that 60 minutes of ischemia followed by 0, 30, or 120 minutes of reperfusion decreases both cytosolic and mitochondrial levels of glutathione in the rat kidney.Department of Physiology and Health Science
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Du, Plessis Elizabeth C. "Pathological investigation of the nephrotoxic effects of the shrub Nolletia gariepina (DC) Mattf. in cattle." Diss., University of Pretoria, 2004. http://hdl.handle.net/2263/23005.
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The first recorded outbreak of nephrotoxicosis induced by the shrub Nolletia gariepina is reported. The outbreaks occurred in cattle in the Kalahari sandveld of South Africa. The toxicosis was experimentally reproduced, initially in a steer, as a pilot trial to confirm toxicity of the plant material, and thereafter in two other cattle. Toxicity was induced by intraruminal administration of 3 g/kg dried, milled plant material as a single dose. The animals had to be starved for 24 hours before dosing, as dosing on a full rumen did not induce any signs of toxicity during five days of observation and clinical pathology monitoring. In both the field outbreaks and the experimental toxicological trial, clinical signs were not specific and varied according to the duration (acute versus subacute) of the toxicological process. Clinical pathological parameters in the experimental cases indicated renal and, to a lesser extent, hepatic damage, with raised serum concentrations of urea, creatinine, aspartate aminotransferase (AST) and gamma glutamyl transferase (GGT). Increased urinary sodium and potassium concentration and GGT activity, as well as proteinuria, were evident. The histological and electron microscopical examinations revealed acute renal tubular epithelial cell degeneration and necrosis, especially of the proximal convoluted tubules. Mild hepatocellular degeneration was also noticeable.Dissertation (MMedVet (Pathology))--University of Pretoria, 2004.
Paraclinical Sciences
unrestricted
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Wang, Amy (Hui-Shan). "The Effects Of Mercuric Chloride On Cultured Atlantic Spotted Dolphin (Stenella Plagiodon) Renal Cells And The Role Of Selenium In Protection." Thesis, Virginia Tech, 1998. http://hdl.handle.net/10919/9777.
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Marine mammals are known for their low susceptibility to mercury toxicity, and it was hypothesized that selenium may play a role in protection against mercury toxicity. To gain insight into the mechanisms of the low susceptibility of cetaceans, we investigated the in vitro effects (1) of mercuric chloride (HgCl₂) on the ultrastructure and cell death of Atlantic spotted dolphin renal cells (Sp1K cells), (2) of HgCl₂ on the cell proliferation and cell cycle status of Sp1K and Rhesus monkey renal cells (MK2), and (3) of sodium selenite (Na₂SeO₃) on cell proliferation and cell death of control and HgCl₂-treated Sp1K cells.
HgCl₂ affected multiple organelles and nuclei in Sp1K cells, and induced apoptosis in a time-and dose-dependent manner. Both ultrastructural changes and induction of apoptosis were milder than seen in other cell types in previous publications. In addition, Sp1K cells were able to proliferate at 25 µM HgCl₂ while MK2 cells were killed at 15 µM HgCl₂. An increase in percentage of cells in the G0/G1 phase in the cell cycle and a decrease in S, and G2/M phase cells were seen in Sp1K cells exposed to more than 10 uM HgCl₂ more than 72 hours. MK2 cells showed cell cycle changes only at 24 hours exposure, and may be due to a sensitive subgroup. These data suggested that Sp1K cells were less susceptible than other cell types in a cell-specific way, which was independent of selenium protection.
Concurrent exposure to Na₂SeO₃ provided protection against the HgCl₂-induced decrease in cell proliferation of Sp1K. The protective effects were greater if Na₂SeO₃ and HgCl₂ were premixed, but disappeared if exposures did not overlap. Although pretreatments with Na₂SeO₃ alone did not provide protection, they increased the protection of selenium administered later. Furthermore, Na₂SeO₃ decreased HgCl₂-induced apoptosis. These data demonstrated the Na₂SeO₃ protection against HgCl₂ toxicity in Sp1K cells in terms of cell proliferation and apoptosis.
This study is the first report that reveals the existence of mercury-selenium antagonism in cultured cetacean cells. The data supported the hypothesis that selenium protection against mercury toxicity is, at least partially, through competition of binding sites and formation of mercury-selenium complex.Master of Science
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Amora, Daniela Nascimento. "Study about renal effects of Crotalus durissus collilineatus snake venom." Universidade Federal do CearÃ, 2005. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13.
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FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgicoCoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
Crotalus durissus collilineatus is a snake usually found in semideciduous forest, the Cerrado region and its bites constitutes an important health problem. The most serious systemic change and primary cause of death is acute renal failure although the mecanisms of the damaging effects are not totally understood. We investigated the biological effects promoted by Crotalus durissus collilineatus crude venom and its fractions crotoxin and phopholipase A2. The toxic effects of C d collilineatus crude venom were evaluated by the histopathological analysis of organs such as heart, kidney, brain, lung and liver. Wistar rats were inoculated intraperitoneally with C d collilineatus crude venom. The liver showed steatosis and microvacuolation.The other organs showed normal morphological aspects. Renal effects were evaluated by the isolated perfused rat kidney method.The crude venom used at the lowest dose (10Âg) increased perfusion pressure (PP), urinary flow (UF), and glomerular filtration rate (GFR), with maximal effect at 120min (PP: control(120) 110.3+/-3.69; venom(120) 126.8+/-10.2; UF: control(120) 0.19+/-0.03; venom(120) 0.23+/-0.06; GFR: control(120) 0.79+/-0.07; venom(120) 1.17+/-0.4). There was no effect on the percent of sodium tubular transport (%TNa+), the percent of potassium tubular transport (%TK+) and the percent of chloride tubular transport (%TCl-) The highest dose of the crude venom (30Âg) caused a significantly decrease in PP (control(120) 110.3Â3.69; venom(120) 96.7Â8.1), RVR (control(120) 6.42Â0.78; venom(120)4.8Â0.56), UF (control(120) 0.19Â0.03; venom(120) 0.12Â0.01) and GFR (control(120) 0.79Â0.07; venom(120)0.53Â0.09). There was not effect on the percent of electrolytes tubular transport (%TNa+, %TK+ and %TCl-). Crotoxin (10mcg) produced a decrease in GFR (control(120) 0.79Â0.07; crotoxin(120) 0.31Â0.10), while PP, RVR and UF remained stable. Crotoxin also reduced %TK+ (control(120) 69.94Â6.49; crotoxin(120) 33.28Â4.78) and %TCl- (control(120) 79.53Â2.67; crotoxin (120) 64.62Â6.93) with maximal effect at 120min. Kidney perfused with phospholipase A2 (PLA2) showed a decrease in GFR (control(120) 0.79Â0.07; PLA2 (120) 0.52Â0.07) at 120min, whereas PP, RVR, UF and %TNa+ remained stable. PLA2 also reduced %TK+ (control(120) 69.94Â6.49; PLA2 (120) 56.26Â6.81) and %TCl- (control(60) 82.25Â2.72; PLA2 (60) 75.04Â4.26) at 60min. These results altogether indicate that Crotalus durissus collilineatus venom caused significative alterations in the renal parameters as well as hepatic damage.
A serpente Crotalus durissus collilineatus à encontrada na regiÃo do Cerrado e o acidente causado por esta espÃcie constitui um problema de saÃde pÃblica. A insuficiÃncia renal aguda à a alteraÃÃo sistÃmica mais sÃria, apesar dos seus mecanismos nÃo serem completamente esclarecidos. O objetivo deste trabalho foi estudar os efeitos biolÃgicos produzidos pelo veneno bruto de Crotalus durissus collilineatus e pelas fraÃÃes crotoxina e fosfolipase A2. Foi realizado o estudo da toxicidade aguda do veneno bruto de C d collilineatus, atravÃs da anÃlise histolÃgica de coraÃÃo, cÃrebro, rins, pulmÃes e fÃgado de ratos tratados com doses crescente do veneno. Nesse estudo foi observada a presenÃa de alteraÃÃes hepÃticas como microvacualizaÃÃo e esteatose, enquanto os demais ÃrgÃos apresentaram aspectos normais. Os efeitos renais foram avaliados atravÃs do mÃtodo de perfusÃo de rim isolado de rato. O veneno bruto, usado na dose de 10Âg, causou um aumento na pressÃo de perfusÃo (PP), no fluxo urinÃrio (FU) e no ritmo de filtraÃÃo glomerular (RFG), com efeito mÃximo aos 120min (PP: controle(120) 110,3+/-3,69; veneno(120) 126,8+/-10,2;FU: controle(120) 0,19+/-0,03; veneno(120) 0,23+/-0,06; RFG: controle(120) 0,79+/-0,07; veneno(120) 1,17+/-0,4). Essa dose nÃo produziu alteraÃÃes no transporte tubular de sÃdio (%TNa+), potÃssio (%TK+) e de cloreto (%TCl-). A dose mais elevada de veneno bruto (30Âg) causou um decrÃscimo significativo, com efeito mÃximo, aos 120min, na PP(controle(120) 110,3+/-3,69; veneno(120) 96,7+/-8,1), na RVR (controle(120) 6,42+/-0,78; veneno(120) 4,8+/-0,56), no FU (controle(120) 0,19+/-0,03; veneno(120) 0,12+/-0,01) e no RFG (controle(120) 0,79+/-0,07; veneno(120) 0,53+/-0,09). NÃo ocorreram alteraÃÃes no transporte tubular de eletrÃlitos. A fraÃÃo crotoxina nÃo produziu alteraÃÃes no RFG (controle(120) 0,79+/-0,07; crotoxina(120) 0,31+/-0,10). Esta fraÃÃo tambÃm reduziu os %TK+ (controle(120) 69,94+/-6,49; crotoxina(120) 33,28+/-4,78) e %TCl- (controle(120) 79,53+/-2,67, crotoxina(120) 64,62+/-6,93). O grupo perfundido com FLA2 apresentou um decrÃscimo no RFG (controle(120) 0,79+/-0,07; FLA2 (120) 0,52+/-0,07), enquanto a PP, a RVR, o FU e o %TNa+ permaneceram estÃveis. Foram observadas reduÃÃes no %TK+ aos 120min (controle(120) 69,94+/-6,49; FLA2(120) 56,26+/-6,81) e aos 60min, no %TCl- (controle(60) 82,25+/-2,72; FLA2(60) 75,04+/-4,26). Foi observada degeneraÃÃo hidrÃpico vacuolar e a presenÃa de material proteinÃceo nos tÃbulos renais, na anÃlise histolÃgica dos rins perfundidos tanto com veneno bruto quanto com as fraÃÃes. Estes resultados indicam que o veneno de Crotalus durissus collilineatus causou alteraÃÃes significativas nos parÃmetros renais e nos aspectos morfolÃgicos hepÃticos.
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Goboza, Mediline. "The biochemical effects of Hypoxis hemerocallidea in the kidney and liver of streptozotocin-induced diabetic male Wistar rats." Thesis, Cape Peninisula University of Technology, 2015. http://hdl.handle.net/20.500.11838/2233.
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Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2015.Diabetes mellitus (DM) is an endocrine disorder that is characterised not only by severe hyperglycemia but also altered metabolism of glucose and lipids. It is a major health problem worldwide and its impact is greatly noticed in developing countries due to the lack of adequate medical facilities. Oxidative stress remains the principal factor that actively plays major roles in the onset and progression of diabetes mellitus and its complications. The use of medicinal plants in the treatment of DM has undisputedly gained the attention and interest of researchers throughout the globe mainly because plants have established promising outcomes in the treatment of diabetes. It is evident that the plants’ constituents possess therapeutically potent metabolites that have beneficial effects such as antioxidant, antidiabetic, anticancer, anti-inflammatory and antibacterial activities. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions. H. hemerocallidea is well known for its beneficial medicinal values. In South Africa it is known as the African potato. The main aim of this study was to investigate both the beneficial and also the possible toxic effects of H. hemerocallidea in the kidney and liver tissues of streptozotocin-induced diabetic male Wistar rats by assessing the antioxidant status and selected biochemical parameters in the two studied organs. Diabetes was induced in overnight fasted rats by administration of a single intraperitoneal injection of STZ at a dosage of 50mg/kg in citrate buffer (0.1 M at 4.5 pH). Hyperglycemia was confirmed 72 hours after induction of diabetes using STZ in rats with glucose levels > 15 mmol/l. Treatment with the plants extract commenced on the fourth day after STZ administration via gastric gavage that was done once a day over a 6 week period. The effects of H. hemerocallidea on glucose, body weight, liver and kidney weights, liver function, kidney function and the oxidative status were evaluated after the feeding period.
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Monteagudo, Felix Salvador Emilio. "Studies of the excretion of aluminium by the kidney and the toxic effects of the element on DNA." Doctoral thesis, University of Cape Town, 1991. http://hdl.handle.net/11427/27153.
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Aluminium is an element of increasing clinical importance. It not only has uses as a medicinal substance but also in recent years it has been shown to be the cause of considerable toxicity, particularly in the setting of chronic renal failure. Diseases that have been shown to be associated with aluminium, or in which it has been implicated, include dialysis dementia, renal osteodystrophy and Alzheimer's disease. This thesis has studied aspects of the interaction between aluminium and the kidney. The work has addressed two major issues. Firstly, a study is described where Malvin's stop-flow technique was used to determine any excretory/absorptive tubular site for Al in the pig kidney. Al was found to be excreted in the distal nephron of the pig kidney. Secondly, the toxic effects of Al in vitro on the DNA of pig kidney cell line LLC-PKl were investigated, in an attempt to elucidate some of the mechanisms of toxic action. DNA synthesis was measured using ³H-TdR incorporation. Over increases of both time (9-72 h) and Al concentration (0.01-8.0 mM), ³H-TdR incorporation was diminished. Effects were evident at concentrations as low as 0.05 mM Al. The production of DNA strand breaks was assessed by the increase in size of cell nucleoids (ie DNA in supercoiled form). Nucleoid size was analyzed in a Epics 753 Fluorescence Activated Cell Sorter interfaced with an MDADSII data acquisition and analysis system. After 90 min incubation with Al (over the concentration range 0.001-32 mM), an increase in nucleoid size was noted at concentrations above 0.05 mM. The data demonstrate that Al exerts an effect on kidney cells in vitro which is expressed as diminished DNA synthesis and production of DNA strand breaks. These effects on DNA may have important long-term implications on various disease states associated with Al toxicity.
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Kato, Michiko. "High Pressure Effects on Biomembrance : Structual and Functional Studies of Membrane-Bond Na^{+}, K^{+}-ATPase from Pig Kidney." Kyoto University, 1999. http://hdl.handle.net/2433/181372.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第7966号
農博第1075号
新制||農||786(附属図書館)
学位論文||H11||N3300(農学部図書室)
UT51-99-M271
京都大学大学院農学研究科農芸化学専攻
(主査)教授 林 力丸, 教授 清水 昌, 教授 松野 隆一
学位規則第4条第1項該当
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Kinnunen, A. (Aino). "Collagen XVIII regulates basement membrane integrity:specific effects of its isoforms on the choroid plexus, kidney and hair follicle." Doctoral thesis, Oulun yliopisto, 2011. http://urn.fi/urn:isbn:9789514294112.
Full textAbstract:
Abstract Collagen XVIII is a multidomain basement membrane proteoglycan with three tissue-specific isoforms. Endostatin, the C-terminal part of collagen XVIII, has antiangiogenic properties, while the frizzled-like domain of the longest isoform is suggested to be capable of inhibiting the Wnt/β-catenin signaling network. This study utilized several genetically modified mouse lines and electron microscopy to achieve new information on the biological role of collagen XVIII, its different isoforms, and the frizzled domain. Lack of collagen XVIII was found to affect the integrity of basement membranes of various tissues, leading to an abnormally loosened network structure. In the choroid plexus, the change in the basement membrane ultrastructure caused alterations in the production of the cerebrospinal fluid and predisposed to the development of hydrocephalus. In the kidney, broadening of the proximal tubular basement membrane was shown to be due specifically to the lack of the short isoform, while the lack of the two longer isoforms led to podocyte foot process effacement. Moreover, lack of collagen XVIII was found to cause softening of the kidney glomeruli and the levels of serum creatinine were elevated in the mutant animals, indicating altered kidney function. The hair follicle cycle was used as a model to study the possible role of the frizzled domain of collagen XVIII in the Wnt/β-catenin signaling cascade. The longer collagen XVIII isoforms were shown to be expressed in the basement membrane facing the dermal papilla and in the hair follicle bulge, containing the follicular stem cells. Lack of the long isoforms led to abnormalities in the progression of the first hair cycle, and the phenotype could be rescued via transgenic delivery of the frizzled domain of the longest isoform, suggesting its involvement in the regulation of the Wnt/β-catening signaling network during the cyclic growth of the hairTiivistelmä Kollageeni XVIII on useista toiminnallisista osista koostuva tyvikalvojen proteoglykaani, jolla on kolme eri kudoksissa esiintyvää isomuotoa. Sen C-terminaalisella endostatiini-osalla on verisuonten kasvua estäviä vaikutuksia, kun taas pisimmän isomuodon frizzled-osan uskotaan estävän Wnt/β-kateniini signalointireitin toimintaa. Tässä tutkimuksessa saatiin uutta tietoa kollageeni XVIII:n, sen eri isomuotojen sekä frizzled-osan biologisesta merkityksestä useiden geenimuunneltujen hiirimallien sekä elektronimikroskopian avulla. Kollageeni XVIII:n puutoksen todettiin vaikuttavan tyvikalvojen rakenteen eheyteen useissa eri kudoksisssa, johtaen epänormaalisti löyhtyvään verkkorakenteeseen. Suonipunoksessa tämä tyvikalvon hienorakenteen muutos vaikutti aivo-selkäydinnesteen tuottumiseen ja altisti vesipään kehittymiselle. Munuaisessa proksimaalisen munuaistiehyen tyvikalvon levenemisen osoitettiin johtuvan lyhyen isomuodon puutoksesta, kun taas kahden pidemmän isomuodon puuttuminen aiheutti podosyyttien jalkalisäkkeiden leviämistä. Lisäksi kollageeni XVIII:n puuttumisen osoitettiin johtavan hiirimallien munuaiskerästen pehmenemiseen sekä veren kreatiniinitason kohoamiseen, viitaten munuaistoiminnan häiriöihin. Karvatuppien syklistä kasvua käytettiin mallina tutkittaessa kollageeni XVIII:n frizzled-osan mahdollisia vaikutuksia Wnt/β-kateniini signalointireittiin. Pidempien kollageeni XVIII isomuotojen osoitettiin tuottuvan karvanystyn tyvikalvossa sekä karvatupin kantasolut sisältävällä pullistuma-alueella. Pitkien isomuotojen puuttuminen johti karvojen ensimmäisen kasvukierron epänormaaliin etenemiseen. Tämä voitiin estää siirtogeenisen frizzled-osan avulla, mikä viittasi sen osallisuuteen Wnt/β-kateniini signalointireitin säätelyyn karvan syklisen kasvun aikana