The proximal tubule of the renal cortical nephron is highly susceptible to intoxication by chemical agents. An in vitro system was developed to study directly the effects of nephrotoxic chemicals on this renal sub-organ fraction without the complication of extrarenal factors. Segments of proximal tubules were isolated by a mechanical method from the kidneys of young rabbits. Tubules obtained by this method retained biochemical, functional, and morphological features comparable to those existing in vivo. Preliminary acute susceptibility studies demonstrated that the isolated proximal tubule segments were sensitive to a variety of known nephrotoxic agents that target the proximal tubule. These agents include halogenated hydrocarbons, heavy metals, and a halogenated vinyl cysteine conjugate. Incubation conditions were optimized to maintain the viability of proximal tubule suspensions for up to four hours. Longer incubation times made it possible to establish a chronology of early tubule responses to chemical intoxication. Long term incubation of proximal tubule suspensions with two model nephrotoxins, cadmium chloride and S-(trans-1,2-dichlorovinyl)-L-cysteine, produced in vitro tubule response patterns similar to those reported in vivo for these agents. While not entirely representative of in vivo exposure conditions, suspensions of isolated proximal tubules are an easily obtained system that proved equally applicable as a screening technique for nephrotoxic compounds or as an in vitro system for delineating proximal tubule response to chemical insult.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/183785 |
| Date | January 1986 |
| Creators | RYLANDER, LESLIE ANN. |
| Contributors | Gandolfi, A. Jay, Brendel, Klaus, Sipes, I. Glenn, Clayton, J. Wesley, Wright, Stephan |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | text, Dissertation-Reproduction (electronic) |
| 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. |
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