Persistent Link:
http://hdl.handle.net/10150/186739
Title:
Toxicity and transport of organic cations in the rabbit kidney.
Author:
Sheevers, Hilary Victoria.
Issue Date:
1994
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The kidney is often the target of toxicants, although the precise mechanisms of nephrotoxicity are often not clear. Renal transport is an important part of toxic mechanisms, and transport, especially of organic cations, has not been well incorporated into nephrotoxicity studies. The transport of anionic toxins into target cells has been shown to be crucial in producing toxicity in renal cortical slices. However, organic cations and their transport in renal toxicity have not been fully examined. Only a small amount of information exists on organic cation nephrotoxicity and transport. This investigation represents a step in developing a greater understanding of nephrotoxic mechanisms associated with organic cations and their transport in the rabbit renal cortex. Model organic cations were first evaluated, and the investigation then focused on one, 1-benzyl quinolinium (BQ). BQ, chosen as the model compound due to its nephrotoxic potential and its interactions at the organic cation transporter, was studied in renal cortical slices, proximal tubules in suspension, and in cortical mitochondria. Toxicity studies demonstrated that BQ was nephrotoxic, and site specific toxicity was noted at the proximal tubule using light microscopy. The effects of BQ on mitochondrial preparations and tubules in suspension suggested that BQ uncoupled mitochondrial oxidative phosphorylation. Studies in slices indicated BQ had great affinity for the organic cation transporter site. Follow-up evaluations using fluorometric quantification suggested that BQ accumulation involves the organic cation transporter; and that BQ may be taken up by both active and passive transport mechanisms. Understanding the toxicity and transport of cations like BQ will help determine the mechanisms associated with organic cation nephrotoxicity and may be used to facilitate the application of transport parameters to prevent toxicity of nephrotoxic cations.
Type:
text; Dissertation-Reproduction (electronic)
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Gandolfi, A. Jay

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleToxicity and transport of organic cations in the rabbit kidney.en_US
dc.creatorSheevers, Hilary Victoria.en_US
dc.contributor.authorSheevers, Hilary Victoria.en_US
dc.date.issued1994en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe kidney is often the target of toxicants, although the precise mechanisms of nephrotoxicity are often not clear. Renal transport is an important part of toxic mechanisms, and transport, especially of organic cations, has not been well incorporated into nephrotoxicity studies. The transport of anionic toxins into target cells has been shown to be crucial in producing toxicity in renal cortical slices. However, organic cations and their transport in renal toxicity have not been fully examined. Only a small amount of information exists on organic cation nephrotoxicity and transport. This investigation represents a step in developing a greater understanding of nephrotoxic mechanisms associated with organic cations and their transport in the rabbit renal cortex. Model organic cations were first evaluated, and the investigation then focused on one, 1-benzyl quinolinium (BQ). BQ, chosen as the model compound due to its nephrotoxic potential and its interactions at the organic cation transporter, was studied in renal cortical slices, proximal tubules in suspension, and in cortical mitochondria. Toxicity studies demonstrated that BQ was nephrotoxic, and site specific toxicity was noted at the proximal tubule using light microscopy. The effects of BQ on mitochondrial preparations and tubules in suspension suggested that BQ uncoupled mitochondrial oxidative phosphorylation. Studies in slices indicated BQ had great affinity for the organic cation transporter site. Follow-up evaluations using fluorometric quantification suggested that BQ accumulation involves the organic cation transporter; and that BQ may be taken up by both active and passive transport mechanisms. Understanding the toxicity and transport of cations like BQ will help determine the mechanisms associated with organic cation nephrotoxicity and may be used to facilitate the application of transport parameters to prevent toxicity of nephrotoxic cations.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairGandolfi, A. Jayen_US
dc.contributor.committeememberBrendel, Klausen_US
dc.contributor.committeememberWright, Stephen H.en_US
dc.contributor.committeememberLaird, Hugh E., IIen_US
dc.contributor.committeememberMcQueen, Charlene A.en_US
dc.identifier.proquest9426567en_US
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