Elevated levels of low molecular weight substances in the red cells of some mammalian species imply unsuspected antioxidant strategies

dc.contributor.advisorHarley, Ericen_ZA
dc.contributor.authorDavids, Virginiaen_ZA
dc.date.accessioned2014-07-28T14:57:22Z
dc.date.available2014-07-28T14:57:22Z
dc.date.issued2009en_ZA
dc.description.abstractAn earlier observation by E.H. Harley (supervisor of this thesis) of curious metabolic anomalies in the red cells of black rhinoceros, and in particular a high free tyrosine level, suggested that a range of unusual, but presumeably physiological, processes might be found in mammalian red blood cells. As a follow-up to this, low molecular weight metabolites were examined in a range of mammalian species, using HPLC-based methods to compare levels in red cells with plasma levels. A remarkable interspecies diversity in red cell HPLC profiles was observed, with the unprecedented accumulation of substances including tyrosine, tryptophan, urate, and urate riboside occuring within the red cells of some species. Whereas novel evolutionary adaptations may characterise most of these species-specific variations, the ability of red cells to produce urate is proposed to be an inducible feature common to the red cells of many, or possibly even all, mammalian species. A surprisingly high degree of intraspecies genetic heterogeneity was evident in tyrosine and urate levels within horse, and urate riboside levels within cow red cells. This was in contrast with the greater homogeneity seen in levels of these and other low molecular weight substances in red cells from the other species evaluated. The next phase of investigation addressed the potential function(s) of these soluble substances accumulating within the red cell, particularly relating to a role in antioxidant defense. Using in vitro antioxidant assays such as the 'oxygen radical absorbance' (ORAC) and 'ferrous ion oxidation-xylenol orange' (FOX) assays, results were obtained consistent with a role for these substances as endogenous red cell antioxidants against a variety of reactive species produced by pathophysiological processes in the body. The demonstration that haemoglobin is involved in facilitating some of this activity further substantiates the idea that the red cell may be playing a crucial role in maintaining circulatory redox balance, and hence protecting other tissues from oxidative damage. If indeed such low molecular weight substances contribute to systemic antioxidant activity in some mammalian species, then apart from the intrinsic interest of such unexpected biological phenomena, these findings could pave the way for a plethora of further investigations, geared towards potential clinical applications (eg. as biomarkers or therapeutic approaches) in human and/or veterinary conditions associated with oxidative stress.en_ZA
dc.identifier.apacitationDavids, V. (2009). <i>Elevated levels of low molecular weight substances in the red cells of some mammalian species imply unsuspected antioxidant strategies</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from http://hdl.handle.net/11427/3162en_ZA
dc.identifier.chicagocitationDavids, Virginia. <i>"Elevated levels of low molecular weight substances in the red cells of some mammalian species imply unsuspected antioxidant strategies."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2009. http://hdl.handle.net/11427/3162en_ZA
dc.identifier.citationDavids, V. 2009. Elevated levels of low molecular weight substances in the red cells of some mammalian species imply unsuspected antioxidant strategies. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Davids, Virginia AB - An earlier observation by E.H. Harley (supervisor of this thesis) of curious metabolic anomalies in the red cells of black rhinoceros, and in particular a high free tyrosine level, suggested that a range of unusual, but presumeably physiological, processes might be found in mammalian red blood cells. As a follow-up to this, low molecular weight metabolites were examined in a range of mammalian species, using HPLC-based methods to compare levels in red cells with plasma levels. A remarkable interspecies diversity in red cell HPLC profiles was observed, with the unprecedented accumulation of substances including tyrosine, tryptophan, urate, and urate riboside occuring within the red cells of some species. Whereas novel evolutionary adaptations may characterise most of these species-specific variations, the ability of red cells to produce urate is proposed to be an inducible feature common to the red cells of many, or possibly even all, mammalian species. A surprisingly high degree of intraspecies genetic heterogeneity was evident in tyrosine and urate levels within horse, and urate riboside levels within cow red cells. This was in contrast with the greater homogeneity seen in levels of these and other low molecular weight substances in red cells from the other species evaluated. The next phase of investigation addressed the potential function(s) of these soluble substances accumulating within the red cell, particularly relating to a role in antioxidant defense. Using in vitro antioxidant assays such as the 'oxygen radical absorbance' (ORAC) and 'ferrous ion oxidation-xylenol orange' (FOX) assays, results were obtained consistent with a role for these substances as endogenous red cell antioxidants against a variety of reactive species produced by pathophysiological processes in the body. The demonstration that haemoglobin is involved in facilitating some of this activity further substantiates the idea that the red cell may be playing a crucial role in maintaining circulatory redox balance, and hence protecting other tissues from oxidative damage. If indeed such low molecular weight substances contribute to systemic antioxidant activity in some mammalian species, then apart from the intrinsic interest of such unexpected biological phenomena, these findings could pave the way for a plethora of further investigations, geared towards potential clinical applications (eg. as biomarkers or therapeutic approaches) in human and/or veterinary conditions associated with oxidative stress. DA - 2009 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Elevated levels of low molecular weight substances in the red cells of some mammalian species imply unsuspected antioxidant strategies TI - Elevated levels of low molecular weight substances in the red cells of some mammalian species imply unsuspected antioxidant strategies UR - http://hdl.handle.net/11427/3162 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/3162
dc.identifier.vancouvercitationDavids V. Elevated levels of low molecular weight substances in the red cells of some mammalian species imply unsuspected antioxidant strategies. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2009 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/3162en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Clinical Laboratory Sciencesen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherClinical Laboratory Sciencesen_ZA
dc.titleElevated levels of low molecular weight substances in the red cells of some mammalian species imply unsuspected antioxidant strategiesen_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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