MECHANISMS UNDERLYING REGIOSELECTIVE ACUTE TUBULAR NECROSIS OF RENAL PROXIMAL TUBULAR SEGMENTS.

Persistent Link:
http://hdl.handle.net/10150/184162
Title:
MECHANISMS UNDERLYING REGIOSELECTIVE ACUTE TUBULAR NECROSIS OF RENAL PROXIMAL TUBULAR SEGMENTS.
Author:
RUEGG, CHARLES EDWARD.
Issue Date:
1987
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 convoluted (CPT) and straight (SPT) portions of the renal proximal tubule are susceptible to injury by a wide variety of chemical agents. These agents often affect the CPT or SPT selectively by proposed mechanisms usually attributed to tubular concentration, blood flow delivery patterns and tubuloglomerular feedback responses within the intact kidney. The innate cellular responses to chemical exposures remain virtually unexplored. Hence, the basic goal of this research was to develop an in vitro system that was conducive to examining the innate cellular differences in susceptibility between the CPT and SPT following in vitro exposure to mercuric chloride (HgCl₂), potassium dichromate (K₂Cr₂O₇)$ or hypoxic conditions. A renal cortical slicing technique was developed for these studies to position the CPT and SPT within discrete regions of slices made perpendicular to the cortical-papillary axis. An incubation vessel that could maintain the morophological and biochemical viability of slices for at least 12 hr was also developed. The selective necrosis of CPT induced by K₂Cr₂O₇ or hypoxic exposure, and SPT induced by HgCl₂, observed in vivo was reproduced in renal cortical slices exposed in vitro. Innate cellular uptake mechanisms were then investigated since the tissue distribution of each metal was found to be most concentrated within their respective injured cell type. The transport of PAH, TEA, phosphate, sulfate, glutathione and cysteine were examined as potential mechanisms for selective accumulation of these metals. K₂Cr₂O₇ caused a dose-dependent reduction in the uptake rate of sulfate by cortical slices, while phosphate, PAH, and TEA uptake were unaffected. Although HgCl₂ has a high affinity for sulfhydryl groups its uptake as a complex to glutathione or cysteine was not enhanced. HgCl₂ also had no affect on the uptake rate of PAH or TEA even though both HgCl₂ and K₂Cr₂O₇ were able to reduce the steady state accumulation of these organic substrates.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Kidney tubules -- Wounds and injuries.; Kidneys -- Necrosis.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicoloy; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Gandolfi, A. Jay

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleMECHANISMS UNDERLYING REGIOSELECTIVE ACUTE TUBULAR NECROSIS OF RENAL PROXIMAL TUBULAR SEGMENTS.en_US
dc.creatorRUEGG, CHARLES EDWARD.en_US
dc.contributor.authorRUEGG, CHARLES EDWARD.en_US
dc.date.issued1987en_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 convoluted (CPT) and straight (SPT) portions of the renal proximal tubule are susceptible to injury by a wide variety of chemical agents. These agents often affect the CPT or SPT selectively by proposed mechanisms usually attributed to tubular concentration, blood flow delivery patterns and tubuloglomerular feedback responses within the intact kidney. The innate cellular responses to chemical exposures remain virtually unexplored. Hence, the basic goal of this research was to develop an in vitro system that was conducive to examining the innate cellular differences in susceptibility between the CPT and SPT following in vitro exposure to mercuric chloride (HgCl₂), potassium dichromate (K₂Cr₂O₇)$ or hypoxic conditions. A renal cortical slicing technique was developed for these studies to position the CPT and SPT within discrete regions of slices made perpendicular to the cortical-papillary axis. An incubation vessel that could maintain the morophological and biochemical viability of slices for at least 12 hr was also developed. The selective necrosis of CPT induced by K₂Cr₂O₇ or hypoxic exposure, and SPT induced by HgCl₂, observed in vivo was reproduced in renal cortical slices exposed in vitro. Innate cellular uptake mechanisms were then investigated since the tissue distribution of each metal was found to be most concentrated within their respective injured cell type. The transport of PAH, TEA, phosphate, sulfate, glutathione and cysteine were examined as potential mechanisms for selective accumulation of these metals. K₂Cr₂O₇ caused a dose-dependent reduction in the uptake rate of sulfate by cortical slices, while phosphate, PAH, and TEA uptake were unaffected. Although HgCl₂ has a high affinity for sulfhydryl groups its uptake as a complex to glutathione or cysteine was not enhanced. HgCl₂ also had no affect on the uptake rate of PAH or TEA even though both HgCl₂ and K₂Cr₂O₇ were able to reduce the steady state accumulation of these organic substrates.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectKidney tubules -- Wounds and injuries.en_US
dc.subjectKidneys -- Necrosis.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology and Toxicoloyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorGandolfi, A. Jayen_US
dc.identifier.proquest8726821en_US
dc.identifier.oclc699799288en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.