Ochratoxins are a group of nephrotoxins produced by a variety of moulds and were first described in 1965 [1]. Dietary exposure to ochratoxins represents a serious health issue and has been associated with several human and animal diseases including porcine nephropathy, Human Endemic Nephropathies and urinary tract tumours in humans. More than 20 years ago, ochratoxin A (OTA) - the most prominent member of this toxin family - was shown to be carcinogenic in rodents and since then extensive research has been performed in order to investigate whether OTA acts by a DNA reactive mode of action. Only recently, this theory has been conclusively disproven and a non-genotoxic mechanism is currently widely accepted for renal toxicity and carcinogenicity of OTA. The work presented in this thesis contributed to this field of science in various ways. First of all, new renal in vitro models were established and existing models were improved for the investigation of renal ochratoxin toxicity. Using these models, the in vitro effects of various OTA exposure scenarios were investigated and endpoints included amongst others general cytotoxicity, cell cycle analysis, protein binding and toxin transport. In all of these studies, distinct species- and sex-differences were observed which mirrored the observed effects in vivo described in literature. Furthermore, the differential toxicity of ochratoxin group members was investigated, the results of which inferred a need for specific detection of OTA and OTB. Due to the lack of such a detection tool, a new, highly specific and sensitive OTB-ELISA was successfully developed based on an OTB-specific monoclonal antibody produced and characterised in our laboratory. This tool allows screening of OTB in food and feed products, which will further improve detection and risk assessment. All of these studies contributed to the elucidation of the underlying mechanisms of ochratoxin toxicity. Therefore, this thesis can be seen as a fundamental part of a paradigm change on our understanding of how ochratoxins exert their harmful long-term effects in humans and animals, thus elucidating the ochratoxin enigma.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:644895 |
| Date | January 2015 |
| Creators | Heussner, Alexandra H. |
| Publisher | University of Sunderland |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://sure.sunderland.ac.uk/5335/ |
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