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dc.contributor.supervisorJha, Awadhesh
dc.contributor.authorBaron, Matthew Graham Joesph
dc.contributor.otherFaculty of Science and Engineeringen_US
dc.date.accessioned2014-05-13T13:39:29Z
dc.date.available2014-05-13T13:39:29Z
dc.date.issued2014
dc.identifier771358en_US
dc.identifier.urihttp://hdl.handle.net/10026.1/3009
dc.descriptionFull version unavailable due to 3rd party copyright restrictions.
dc.description.abstract

Regulatory and academic studies use large numbers of fish annually. The use of fish primary cells offers an in vitro alternative for the assessment of chemical toxicity and the evaluation of environmental samples in ecotoxicology. Their uses however are not without limitations which includes short culture periods (i.e. longevity and loss of organ-specific functionality over time. Three-dimensional (3-D spheroid) technology is now established for in vitro mammalian toxicity studies and offers significant advantages for environmental applications in a model fish species. This thesis reports development of a reproducible six-well plate, gyratory-mediated method for rainbow trout (Oncorhynchus mykiss) hepatocyte spheroid culture and compares morphological, functional and biochemical status with two-dimensional (2-D) monolayer hepatocytes. The work further assesses the bio-transformation potential of developed 3-D spheroids to a range of environmentally relevant pharmaceuticals. The study suggests that mature spheroids retain some organotypic responses over-time in culture including morphological (viz., smooth outer surface, tight cell–cell contacts); functional (viz., histo-architecture; cell adhesion molecule expression) and biochemical properties (viz., protein, glucose, albumin- and enzyme levels) that is superior to conventional 2-D monolayer cells. These 3-D spheroids also demonstrate a capacity for the metabolism of environmentally-relevant pharmaceuticals that could be utilised to better understand their bio-accumulation potential in fish. This is an important step forward for developing alternative in vitro tools in future fish ecotoxicological studies as well as for fundamental understanding of the interaction of chemicals with biomolecules which could potentially lead to detrimental responses at different levels of biological organisation.

en_US
dc.description.sponsorshipBBSRC, AstraZenecaen_US
dc.language.isoenen_US
dc.publisherPlymouth Universityen_US
dc.subjectFishen_US
dc.subjectAlternativesen_US
dc.subject3-Den_US
dc.subjectEnvironmenten_US
dc.subjectPhysiologyen_US
dc.subjectToxicologyen_US
dc.subjectMetabolismen_US
dc.titleDevelopment and characterisation of a three-dimensional in vitro hepatic fish model to investigate xenobiotic metabolismen_US
dc.typeThesis
plymouth.versionEdited versionen_US
dc.identifier.doihttp://dx.doi.org/10.24382/4863


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