Studies of the excretion of aluminium by the kidney and the toxic effects of the element on DNA

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dc.contributor.advisorFolb, Peter Ien_ZA
dc.contributor.authorMonteagudo, Felix Salvador Emilioen_ZA
dc.date.accessioned2018-01-30T14:03:51Z
dc.date.available2018-01-30T14:03:51Z
dc.date.issued1991en_ZA
dc.description.abstractAluminium 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.en_ZA
dc.identifier.apacitationMonteagudo, F. S. E. (1991). <i>Studies of the excretion of aluminium by the kidney and the toxic effects of the element on DNA</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology. Retrieved from http://hdl.handle.net/11427/27153en_ZA
dc.identifier.chicagocitationMonteagudo, Felix Salvador Emilio. <i>"Studies of the excretion of aluminium by the kidney and the toxic effects of the element on DNA."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology, 1991. http://hdl.handle.net/11427/27153en_ZA
dc.identifier.citationMonteagudo, F. 1991. Studies of the excretion of aluminium by the kidney and the toxic effects of the element on DNA. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Monteagudo, Felix Salvador Emilio AB - 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. DA - 1991 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 1991 T1 - Studies of the excretion of aluminium by the kidney and the toxic effects of the element on DNA TI - Studies of the excretion of aluminium by the kidney and the toxic effects of the element on DNA UR - http://hdl.handle.net/11427/27153 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/27153
dc.identifier.vancouvercitationMonteagudo FSE. Studies of the excretion of aluminium by the kidney and the toxic effects of the element on DNA. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Clinical Pharmacology, 1991 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/27153en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherAluminum - adverse effectsen_ZA
dc.subject.otherAluminum - toxicityen_ZA
dc.subject.otherDNA - Biosynthesisen_ZA
dc.subject.otherKidney - secretionen_ZA
dc.titleStudies of the excretion of aluminium by the kidney and the toxic effects of the element on DNAen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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