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Proteomic assessment of potential in vitro hepatotoxicity models

Thesis (PhD)--University of Pretoria, 2016.

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Other Authors: Cromarty, Allan Duncan
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Published: University of Pretoria 2017
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access_status_str Open Access
author2 Cromarty, Allan Duncan
author_browse Cromarty, Allan Duncan
author_facet Cromarty, Allan Duncan
collection Thesis
dc_rights_str_mv © 2017 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria.
description Thesis (PhD)--University of Pretoria, 2016.
format Thesis
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institution University of Pretoria (South Africa)
last_indexed 2026-06-10T12:38:00.699Z
license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository
publishDate 2017
publishDateRange 2017
publishDateSort 2017
publisher University of Pretoria
publisherStr University of Pretoria
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source_str UPSpace — University of Pretoria Institutional Repository
spelling oai:repository.up.ac.za:2263/59107 Proteomic assessment of potential in vitro hepatotoxicity models Cromarty, Allan Duncan Lilley, Kathryn S. Hurrell, Tracey Health sciences theses SDG-03 Health sciences theses SDG-17 Thesis (PhD)--University of Pretoria, 2016. Scientifically credible and valid biological systems are essential in pharmaceutical research and development. Standardizing in vitro preclinical hepatotoxicity is confounded by the diversity of origin of cells and the ability to retain hepatocellular functions. Key determinants of valid hepatotoxicity models are resemblance to primary human hepatocytes (PHHs), adaptability to high-throughput screening and biological applicability. Numerous in vitro models, including immortalized cell lines and hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells (iPSCs), attempt to reflect features of PHH. Additional influencing factors are the mechanical and geometric environment which dictate functionality and suggest a role for spatial organization as a requirement for mimicking PHH. As there is poor correlation between the cellular genome and proteome, assessing the hepatic phenotypes using proteomics is essential to capture functional cellular responses. The aim of this research was to determine proteomic differences between PHHs and differentially cultured and sourced human hepatocyte-derived cell lines or differentiated HLCs. Additionally, hepatocyte models were used to generate non-specific, proteome-wide information associated with exposure to selected known hepatotoxins to identify potential proteomic signatures of hepatotoxicity. em2026 Pharmacology PhD Unrestricted SDG-03: Good health and well-being SDG-17: Partnerships for the goals 2017-02-20T06:32:26Z 2017-02-20T06:32:26Z 2017-05-05 2016 Thesis Hurrell, T 2016, Proteomic assessment of potential in vitro hepatotoxicity models, PhD Thesis, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/59107> A2017 http://hdl.handle.net/2263/59107 © 2017 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria
spellingShingle Health sciences theses SDG-03
Health sciences theses SDG-17
Proteomic assessment of potential in vitro hepatotoxicity models
title Proteomic assessment of potential in vitro hepatotoxicity models
title_full Proteomic assessment of potential in vitro hepatotoxicity models
title_fullStr Proteomic assessment of potential in vitro hepatotoxicity models
title_full_unstemmed Proteomic assessment of potential in vitro hepatotoxicity models
title_short Proteomic assessment of potential in vitro hepatotoxicity models
title_sort proteomic assessment of potential in vitro hepatotoxicity models
topic Health sciences theses SDG-03
Health sciences theses SDG-17
url http://hdl.handle.net/2263/59107