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Effects of inorganic mercury on developing zebrafish (Danio rerio) larvae

dc.contributor.advisorGeorge, Graham N.en_US
dc.contributor.advisorKrone, Patrick H.en_US
dc.contributor.committeeMemberPickering, Ingrid J.en_US
dc.contributor.committeeMemberJanz, David M.en_US
dc.contributor.committeeMemberPaterson, Phyllis G.en_US
dc.contributor.committeeMemberBlakley, Barry R.en_US
dc.creatorMacDonald, Tracyen_US
dc.date.accessioned2015-09-30T12:00:18Z
dc.date.available2015-09-30T12:00:18Z
dc.date.created2015-10en_US
dc.date.issued2015-09-29en_US
dc.date.submittedOctober 2015en_US
dc.description.abstractMercury (Hg) compounds are some of the most toxic compounds of any heavy metal on earth. Due to long-range transport from point sources Hg can be found world-wide in air, soil, water, and living organisms. Mercury compounds can cause a number of adverse effects, with the unborn fetus, infants, and children being most susceptible. Zebrafish (Danio rerio) are an excellent vertebrate model system for toxicological studies, including developmental effects. The overall objective of this research was to investigate the effects of inorganic forms of Hg in zebrafish larvae. Unique accumulation patterns were observed using synchrotron X-ray fluorescence imaging after zebrafish were exposed to one of four Hg compounds (i.e. mercuric chloride, mercury bis-L-cysteineate, methylmercury chloride, methylmercury L-cysteineate). Specifically, we noted chemical form dependant and tissue-specific Hg accumulation including the sensory cells of the olfactory epithelia and the neuromasts. Phenylthiourea (PTU) is commonly used to block zebrafish melanogenesis to generate transparent larvae to aid with enhanced visualization of immunohistochemical and vital stains. It was determined that PTU dramatically alters Hg toxicity through chemical interaction with Hg so that further studies were conducted in the absence of PTU. To investigate the effects of Hg on primary neurons, the immunohistochemistry protocol using anti-acetylated tubulin was performed and the results demonstrated that mercuric chloride damages primary neurons particularly in the olfactory pits. To study potential detoxification of Hg in zebrafish we examined the efficacy of two sequestration agents, dimercaptosuccinic acid and alpha lipoic acid, as well as endogenous selenium. The levels of Hg were not significantly lower following treatment with either sequestration agent under the conditions used in this research. Previous work examining the antagonistic relationship between Hg and selenium has been conducted by dosing animals with both Hg and selenium (Se). We discovered a mixed chalcogenide of the general form HgSxSe(1-x) forming in vivo following exposure to mercuric chloride without the addition of selenium. Indeed the selenium may have been remobilized from natural stores in the pigment spots. The research presented herein demonstrates that the target tissues for Hg depend strongly on chemical form. In particular inorganic Hg can accumulate in a number of important tissues including sensory systems. The formation of insoluble and non-toxic HgSxSe(1-x) in zebrafish larvae suggests that endogenous selenium may play critical roles in modulating toxicity.en_US
dc.identifier.urihttp://hdl.handle.net/10388/ETD-2015-10-2243en_US
dc.language.isoengen_US
dc.subjectzebrafish larvaeen_US
dc.subjectinorganic mercuryen_US
dc.subjectorganic mercuryen_US
dc.subjectsynchrotron techniquesen_US
dc.subjectX-ray fluorescence imagingen_US
dc.subjectdevelopmenten_US
dc.titleEffects of inorganic mercury on developing zebrafish (Danio rerio) larvaeen_US
dc.type.genreThesisen_US
dc.type.materialtexten_US
thesis.degree.departmentToxicology Centreen_US
thesis.degree.disciplineToxicologyen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophy (Ph.D.)en_US

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