Development and validation of lung slices as an in vitro model for pulmonary toxicity studies.

Persistent Link:
http://hdl.handle.net/10150/185594
Title:
Development and validation of lung slices as an in vitro model for pulmonary toxicity studies.
Author:
Stefaniak, Mary Suzanne.
Issue Date:
1991
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:
In light of the increasing emphasis on in vitro techniques for toxicologic research, a new model system was developed for preparation and short term maintenance of mammalian lung slice in dynamic organ culture. Viability of explanted tissue, characterized by a number of biochemical and histological parameters, was maintained for 5 days in culture. Validation as a toxicologic tool was accomplished by screening a series of classical toxicants (acrolein, nitrofurantoin, paraquat, cyclophosphamide, monocrotaline, bleomycin and amiodarone). Results indicated this in vitro model system can be used to mimic the acute in vivo toxicity of direct-acting compounds, including the production of cell-specific injury. Application to mechanistic study was approached by investigating the toxicity induced by redox cycling compounds. The toxicity of nitrofurantoin and paraquat was enhanced by high O₂ and attenuated by catalase. Evidence of lipid peroxidation was provided by measuring the disappearance of polyunsaturated fatty acids, and by concomitant depletion of vitamin E. NPSH content of slices remained unchanged, suggesting that GSH is not a primary target for these agents.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Dissertations, Academic; Pharmacology; Pathology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Brendel, Klaus

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleDevelopment and validation of lung slices as an in vitro model for pulmonary toxicity studies.en_US
dc.creatorStefaniak, Mary Suzanne.en_US
dc.contributor.authorStefaniak, Mary Suzanne.en_US
dc.date.issued1991en_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.abstractIn light of the increasing emphasis on in vitro techniques for toxicologic research, a new model system was developed for preparation and short term maintenance of mammalian lung slice in dynamic organ culture. Viability of explanted tissue, characterized by a number of biochemical and histological parameters, was maintained for 5 days in culture. Validation as a toxicologic tool was accomplished by screening a series of classical toxicants (acrolein, nitrofurantoin, paraquat, cyclophosphamide, monocrotaline, bleomycin and amiodarone). Results indicated this in vitro model system can be used to mimic the acute in vivo toxicity of direct-acting compounds, including the production of cell-specific injury. Application to mechanistic study was approached by investigating the toxicity induced by redox cycling compounds. The toxicity of nitrofurantoin and paraquat was enhanced by high O₂ and attenuated by catalase. Evidence of lipid peroxidation was provided by measuring the disappearance of polyunsaturated fatty acids, and by concomitant depletion of vitamin E. NPSH content of slices remained unchanged, suggesting that GSH is not a primary target for these agents.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectDissertations, Academicen_US
dc.subjectPharmacologyen_US
dc.subjectPathology.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.advisorBrendel, Klausen_US
dc.contributor.committeememberGandolfi, A. Jayen_US
dc.contributor.committeememberLiebler, Danielen_US
dc.contributor.committeememberHalonen, Marilynen_US
dc.contributor.committeememberLantz, R. Clarken_US
dc.identifier.proquest9200043en_US
dc.identifier.oclc711786166en_US
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