Accumulation, distribution and chemical form of organic mercury in brain tissue and larval zebrafish (Danio rerio)
| dc.contributor.advisor | George, Graham | |
| dc.contributor.advisor | Pickering, Ingrid | |
| dc.contributor.advisor | Krone, Patrick | |
| dc.contributor.committeeMember | Janz, David | |
| dc.contributor.committeeMember | Eames, Brian | |
| dc.contributor.committeeMember | Paterson, Phyllis | |
| dc.contributor.committeeMember | Coulthard, Ian | |
| dc.creator | James, Ashley | |
| dc.date.accessioned | 2021-08-05T02:58:31Z | |
| dc.date.available | 2023-08-04T06:05:06Z | |
| dc.date.created | 2021-10 | |
| dc.date.issued | 2021-08-04 | |
| dc.date.submitted | October 2021 | |
| dc.date.updated | 2021-08-05T02:58:32Z | |
| dc.description.abstract | Compounds of organometallic mercury have been recognized for their toxicity to humans since the mid-1800s. While mercury is a natural constituent of the Earth’s crust, with natural processes resulting in its release into the larger environment, anthropogenic activities including coal combustion and gold mining have increased the global bioavailable mercury burden. Atmospheric mercury can be transported globally, and its transformations between different environmental compartments can result in the formation of toxic organometallic mercury species. These compounds are known to bioaccumulate and biomagnify through trophic levels to animal species which may be consumed by human populations, and which may result in toxicity and even death. The mechanisms by which methylmercury (the most highly studied form of organometallic mercury) exerts its toxicity are many and varied. It is due to these complexities that methylmercury (and inorganic species of mercury) continue to be the focus of a great deal of research. The goal of this research was to advance the prevailing understanding of organometallic mercury through investigation of its toxicity as it relates to chemical speciation, as well as its accumulation and distribution in relation to transportation and defensive mechanisms. To that end, the chemical speciation of mercury in both feline and human cases of historical exposures to organometallic mercury species were studied using X-ray absorption spectroscopy (XAS) and high energy resolution fluorescence detection XAS (HERFD-XAS) to gain insight into the dynamics of mercury in unique samples which did not originate from a model organism. Cases of exposure which would be defined as acute were dominated by varying forms of inorganic mercury, with some remaining organometallic mercury present (in most cases). In contrast, mercury species present in chronic cases of exposure coming from residents of the Seychelles, where a lifetime of consuming fish species which may contain high levels of mercury is the norm, remained entirely organometallic. The implications of this finding are important as most of what is known about mercury poisoning in human populations comes from cases of acute exposure, even while most instances of exposure of humans to mercury occurs at chronic low-levels. Comparisons were also made using XAS between formalin-fixed and frozen brain tissue, as well as cryopreserved and methacrylate embedded zebrafish (Danio rerio) to determine whether samples which had undergone more extensive preservation may be relied upon in studies of chemical form, which has been shown to be highly important in toxicity. Mercury was not observed to be affected by preservation method in terms of speciation in brain tissue or in accumulation and distribution in larval zebrafish. Other endogenous elements, however, were noted to be affected. Both the transportation of methylmercury as well as the mechanisms through which defense against the toxicity of methylmercury occurs are routinely studied. Transportation of methylmercury, currently assumed to occur via L-system transporters, was seen to be affected by compounds likely to compete for uptake. This was demonstrated by increased survival in toxicity studies and reduced concentrations of mercury in target organs using X-ray fluorescence imaging (XFI) of larval zebrafish which had been co-exposed to methylmercury-ʟ-cysteine in the presence of various LAT competitors. Transportation is thought to be primarily stereoselective and indeed, zebrafish exposed to methylmercury-ᴅ-cysteine demonstrated increased survival. Differences in mercury concentrations in target organs between enantiomers were noted but did not prove to be statistically significant. Lastly, an unforeseen target of mercury accumulation was observed using XFI after exposures to various organic and inorganic mercury species: the epithelial layer of larval zebrafish, where mucosal production occurs. Subsequent titrations of organometallic mercury with harvested mucosa examined using XAS demonstrated the occurrence of demethylation which, to our knowledge, has never been seen. While many faceted, the research conducted in this thesis highlights the complexity of mercury and, with the discoveries made herein demonstrates the need for continuing research. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/10388/13504 | |
| dc.subject | methylmercury | |
| dc.subject | chemical form | |
| dc.subject | toxicity | |
| dc.subject | X-ray absorption spectroscopy | |
| dc.subject | X-ray fluorescence imaging | |
| dc.subject | zebrafish larvae | |
| dc.title | Accumulation, distribution and chemical form of organic mercury in brain tissue and larval zebrafish (Danio rerio) | |
| dc.type | Thesis | |
| dc.type.material | text | |
| local.embargo.terms | 2023-08-04 | |
| thesis.degree.department | Western College of Veterinary Medicine | |
| thesis.degree.discipline | Toxicology | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy (Ph.D.) |