Spelling suggestions: "subject:"aquatic toxicology"" "subject:"aquatic toxicologyc""
11 |
Adverse Health Effects of Dietary Selenomethionine on Juvenile White Sturgeon (Acipenser transmontanus)2016 March 1900 (has links)
Sturgeon are an ancient family of fish which have remained essentially unchanged for 200 million years, rendering them physiologically distinct from the more modern teleosts. Of the 26 known species of sturgeons all are likely endangered. North American populations have been declining steadily since the 1800s due to factors such as overharvesting, habitat alterations and increasing pollution. White sturgeon (Acipenser transmontanus), endemic to Western North America, are the largest freshwater fish on the continent. Protecting white sturgeon is of interest because nearly all Canadian populations are endangered and they are culturally and economically important. Factors such as great size, longevity, position in the food chain and benthic life style render white sturgeon particularly susceptible to bioaccumulation of toxicants. They are known to be among the most sensitive species to pollutants such as metal ions, dioxin-like compounds and endocrine disrupters. However, little is known about their susceptibility to other priority contaminants such as selenium (Se). Selenium, in its organic form selenomethionine (SeMet) has become a contaminant of particular concern as it is a known toxicant that efficiently bioaccumulates and biomagnifies in the food chain. It is also of interest as Se is an essential micronutrient that becomes toxic at only marginally greater than optimal doses. Current elevated concentrations of SeMet in white sturgeon prey, with predicted increases in anthropogenic releases, have made it a contaminant of concern for this species. It is hypothesized that increased releases of Se to aquatic environments have contributed in part to sturgeon declines; however, to date little is known about its specific effects on this species. Therefore, the purpose of the present study was to investigate the sensitivity of three year old white sturgeon to dietary SeMet and to link physiological effects to key molecular events of toxicity and to elucidate the mechanism of toxicity. Specifically, this thesis focused on oxidative stress in liver tissue as a hypothesized primary mechanism of toxicity. For 72 days sturgeon were given either a control diet of 1.4 µg Se/g feed or a diet spiked with SeMet (5.6, 22.4 or 104.4 µg Se/g feed dry mass). These doses corresponded to an uptake necessary for proper health, two environmentally relevant exposures, and a worst-case scenario for industrial Se release, respectively. A subsample of fish was taken at day 10 to investigate molecular endpoints. Within 10 days of exposure, pathological effects were observed in fish given the high dose. Occurrence of severe edema causing exophthalmos developed within 15, 23 and 52 days in high, medium and low dose group fish, respectively. There was a 54% and 22% occurrence of lethal effects in the high and medium dose groups, respectively. Se accumulated in a dose dependent manner and reached equilibrium in high dose fish after approximately 40 days. Growth, liver weight and hepatosomatic index were all significantly lower in the high dose group. Histology of 72 day liver samples showed a significant and dose dependent increase in melanomacrophage aggregates and decrease of energy stores and cell size. Food avoidance was also observed in sturgeon exposed to the high dose. To investigate oxidative stress, 10 day liver samples were tested for changes in gene expression coding for glutathione peroxidase (GPx), superoxide dismutase, catalase, glutathione S-transferase, apoptosis inducing factor and caspase 3, using real-time PCR. Only GPx was significantly induced. Day 72 liver samples were tested for the presence of lipid hydroperoxides but there were no significant differences between dose groups and controls, which shed doubt on oxidative stress being the main driver of toxicity. Taken together the data makes a strong case for the sensitivity of white sturgeon to Se accumulation and indicates a general suppression of health due to toxic levels of exposure. However, in contrast to other fish species exposed to Se, oxidative stress is not likely the main mechanism of toxicity in white sturgeon. Findings from the present study could be used for the risk assessment of sturgeon to anthropogenic Se in aquatic ecosystems.
|
12 |
Identification of components in crude oil that are chronically toxic to the early life stages of fishKhan, Colin Winston 02 January 2008 (has links)
The risk of crude oil exposure to the early life stages (ELS) of fish is difficult to assess, given the complexity of the chemical composition of different oils. The aromatic portion of crude oil contains polycyclic aromatic hydrocarbons (PAH), which are known to be toxic. In 2004, an “effects-driven” fractionation research program was initiated in an attempt to better identify toxic constituents of two unique crude oils, Alaskan North Slope Crude (ANSC; medium-heavy crude) and Scotia Light (SCOT; light crude). The ANSC contained much more PAH than SCOT. These oils induced cytochrome P4501A1 (CYP1A) enzymes in juvenile rainbow trout (Oncorhynchus mykiss) and caused blue-sac disease (BSD) and mortality in larval Japanese medaka (Oryzias latipes).
Four unique fractions (F1-F4) were produced from both oils via low temperature vacuum distillation. The F3 contained an array of unsubstituted and alkyl-PAH, and was responsible for most of the CYP1A induction and chronic toxicity associated with whole oil. Cold acetone extraction (CAE) of F3 produced 2 new sub-fractions (F3-1 and F3-2). The F3-1 was rich in alkyl-PAH, was a potent CYP1A inducer, and was chronically toxic to ELS of fish. The F3-1 was further separated into five more sub-fractions via normal phase HPLC (F3-1-1 – F3-1-5). Neither F3-1-1 nor F3-1-2 induced CYP1A or produced BSD, but F3-1-2 was lethal. The F3-1-3, 4, and 5 were all potent CYP1A inducers and were all chronically toxic.
Induction of CYP1A proved to be an effective tool for tracing potentially toxic PAH throughout fractionation (Chapter 2), and sub-fractions rich in alkyl-PAH caused the most BSD and mortality (Chapter 3). Alkyl-homologues of phenanthrene, fluorene, naphthobenzothiophene (NBT), pyrene, and chrysene are perhaps the most toxic of the known constituents present in crude oil. The ANSC sub-fractions were more toxic than the SCOT ones, indicating that heavier crude oils with a higher proportion of intermediate-sized alkyl-PAH may be more toxic than lighter crude oils that are comprised of fewer of these compounds. / Thesis (Master, Biology) -- Queen's University, 2007-12-20 13:18:50.794 / This research was accomplished with funding assistance from the Nationmal Oceanic and Atmospheric Administration (NOAA), Petroleum Research Atlantic Canada (PRAC), Environment Canada, and the Department of Fisheries and Oceans.
|
13 |
Toxicity Evaluation of Gallium- and Indium-Related Chemicals by Using Freshwater Amphipod (Hyalella azteca) and Human Cultured Cells / 淡水性ヨコエビおよびヒト培養細胞を用いたガリウムとインジウム化合物の毒性評価TAN, SHIH WEI 23 March 2022 (has links)
京都大学 / 新制・課程博士 / 博士(工学) / 甲第23867号 / 工博第4954号 / 新制||工||1774(附属図書館) / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 清水 芳久, 教授 米田 稔, 准教授 松田 知成 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM
|
14 |
The Serotonergic System as a Target for Neuroendocrine Disruption in the Brain of Goldfish (Carassius auratus)Mennigen, Jan A. 03 May 2011 (has links)
Serotonin stimulates reproduction and inhibits feeding/growth in the neuroendocrine brain of goldfish. The objective of this thesis is to study the effects of selective serotonin
reuptake inhibitor pharmaceuticals (SSRIs) on these systems, as SSRIs, such as fluoxetine, are detected in effluent and bioconcentrate in the brain of wild fish. Genes of the serotonin system were cloned to identify molecular conservation, seasonal expression, and tissue distribution. The serotonin transporter, the target molecule of fluoxetine, was highly conserved and ubiquitously expressed in goldfish. Seasonal changes of hypothalamic gene expression of the serotonin transporter support a role in the seasonal modulation of both processes. Fluoxetine injection experiments were used to assess effects on reproductive endpoints and to identify molecular mechanisms in the neuroendocrine brain. Fluoxetine inhibited serum estradiol concentrations in female goldfish and decreased isotocin mRNA abundance in the hypothalamus and telencephalon. Isotocin injections stimulated circulating estradiol concentrations, providing a causal link. Evidence for an involvement of serotonin in isotocin regulation was investigated using immunocytochemistry and 5-HT1A receptor agonists and antagonists. A close proximity of
serotonin fibers and isotocin cell bodies and fibers was found in the telencephalon and pituitary,respectively. Injection of a 5-HT1A receptor antagonist inhibited isotocin mRNA expression in the telencephalon. Identified gene targets were investigated in waterborne fluoxetine exposures,including environmental concentrations. Waterborne fluoxetine led to a reduction in basal and pheromone-stimulated milt volume in male goldfish. Gene expression evidence indicated a central inhibitory effect of fluoxetine through the decrease in mRNA abundance of follicle-stimulating hormone in the pituitary and isotocin in the telencephalon. Feeding rate and weight decreased in fluoxetine-injected goldfish, indicating an anorexigenic effect. Fluoxetine induced changes in the gene expression of the feeding peptides neuropeptide Y, corticotropin-releasing factor, and cocaine- and amphetamine-regulated transcript-I in the hypothalamus and telencephalon. Waterborne exposure to fluoxetine validated the anorexigenic effect in goldfish and was correlated with increased expression of corticotropin-releasing factor mRNA, an anorectic peptide. The thesis provides evidence for disrupting effects of fluoxetine on neuroendocrine control of reproductive
function and feeding/growth in goldfish, partially at environmental concentrations. The thesis provides the framework for the investigation of existing aquatic contaminants which modulate the serotonin system.
|
15 |
The Serotonergic System as a Target for Neuroendocrine Disruption in the Brain of Goldfish (Carassius auratus)Mennigen, Jan A. 03 May 2011 (has links)
Serotonin stimulates reproduction and inhibits feeding/growth in the neuroendocrine brain of goldfish. The objective of this thesis is to study the effects of selective serotonin
reuptake inhibitor pharmaceuticals (SSRIs) on these systems, as SSRIs, such as fluoxetine, are detected in effluent and bioconcentrate in the brain of wild fish. Genes of the serotonin system were cloned to identify molecular conservation, seasonal expression, and tissue distribution. The serotonin transporter, the target molecule of fluoxetine, was highly conserved and ubiquitously expressed in goldfish. Seasonal changes of hypothalamic gene expression of the serotonin transporter support a role in the seasonal modulation of both processes. Fluoxetine injection experiments were used to assess effects on reproductive endpoints and to identify molecular mechanisms in the neuroendocrine brain. Fluoxetine inhibited serum estradiol concentrations in female goldfish and decreased isotocin mRNA abundance in the hypothalamus and telencephalon. Isotocin injections stimulated circulating estradiol concentrations, providing a causal link. Evidence for an involvement of serotonin in isotocin regulation was investigated using immunocytochemistry and 5-HT1A receptor agonists and antagonists. A close proximity of
serotonin fibers and isotocin cell bodies and fibers was found in the telencephalon and pituitary,respectively. Injection of a 5-HT1A receptor antagonist inhibited isotocin mRNA expression in the telencephalon. Identified gene targets were investigated in waterborne fluoxetine exposures,including environmental concentrations. Waterborne fluoxetine led to a reduction in basal and pheromone-stimulated milt volume in male goldfish. Gene expression evidence indicated a central inhibitory effect of fluoxetine through the decrease in mRNA abundance of follicle-stimulating hormone in the pituitary and isotocin in the telencephalon. Feeding rate and weight decreased in fluoxetine-injected goldfish, indicating an anorexigenic effect. Fluoxetine induced changes in the gene expression of the feeding peptides neuropeptide Y, corticotropin-releasing factor, and cocaine- and amphetamine-regulated transcript-I in the hypothalamus and telencephalon. Waterborne exposure to fluoxetine validated the anorexigenic effect in goldfish and was correlated with increased expression of corticotropin-releasing factor mRNA, an anorectic peptide. The thesis provides evidence for disrupting effects of fluoxetine on neuroendocrine control of reproductive
function and feeding/growth in goldfish, partially at environmental concentrations. The thesis provides the framework for the investigation of existing aquatic contaminants which modulate the serotonin system.
|
16 |
The Serotonergic System as a Target for Neuroendocrine Disruption in the Brain of Goldfish (Carassius auratus)Mennigen, Jan A. 03 May 2011 (has links)
Serotonin stimulates reproduction and inhibits feeding/growth in the neuroendocrine brain of goldfish. The objective of this thesis is to study the effects of selective serotonin
reuptake inhibitor pharmaceuticals (SSRIs) on these systems, as SSRIs, such as fluoxetine, are detected in effluent and bioconcentrate in the brain of wild fish. Genes of the serotonin system were cloned to identify molecular conservation, seasonal expression, and tissue distribution. The serotonin transporter, the target molecule of fluoxetine, was highly conserved and ubiquitously expressed in goldfish. Seasonal changes of hypothalamic gene expression of the serotonin transporter support a role in the seasonal modulation of both processes. Fluoxetine injection experiments were used to assess effects on reproductive endpoints and to identify molecular mechanisms in the neuroendocrine brain. Fluoxetine inhibited serum estradiol concentrations in female goldfish and decreased isotocin mRNA abundance in the hypothalamus and telencephalon. Isotocin injections stimulated circulating estradiol concentrations, providing a causal link. Evidence for an involvement of serotonin in isotocin regulation was investigated using immunocytochemistry and 5-HT1A receptor agonists and antagonists. A close proximity of
serotonin fibers and isotocin cell bodies and fibers was found in the telencephalon and pituitary,respectively. Injection of a 5-HT1A receptor antagonist inhibited isotocin mRNA expression in the telencephalon. Identified gene targets were investigated in waterborne fluoxetine exposures,including environmental concentrations. Waterborne fluoxetine led to a reduction in basal and pheromone-stimulated milt volume in male goldfish. Gene expression evidence indicated a central inhibitory effect of fluoxetine through the decrease in mRNA abundance of follicle-stimulating hormone in the pituitary and isotocin in the telencephalon. Feeding rate and weight decreased in fluoxetine-injected goldfish, indicating an anorexigenic effect. Fluoxetine induced changes in the gene expression of the feeding peptides neuropeptide Y, corticotropin-releasing factor, and cocaine- and amphetamine-regulated transcript-I in the hypothalamus and telencephalon. Waterborne exposure to fluoxetine validated the anorexigenic effect in goldfish and was correlated with increased expression of corticotropin-releasing factor mRNA, an anorectic peptide. The thesis provides evidence for disrupting effects of fluoxetine on neuroendocrine control of reproductive
function and feeding/growth in goldfish, partially at environmental concentrations. The thesis provides the framework for the investigation of existing aquatic contaminants which modulate the serotonin system.
|
17 |
Efeitos do Thiodan® (endosulfan) nas brânquias de Astyanax aff. bimaculatus / Effects of Thiodan® (endosulfan) in the gills of Astyanax aff. bimaculatusMoraes, Joelma Crespo 04 August 2011 (has links)
Made available in DSpace on 2015-03-26T13:47:02Z (GMT). No. of bitstreams: 1
texto completo.pdf: 1671012 bytes, checksum: 403ddd0d13dc2890004dae5a13c0606b (MD5)
Previous issue date: 2011-08-04 / One of the factors most relevant in environmental pollution that involves the ecosystem is the contamination by pesticides, especially when these are applied indiscriminately. Between these compounds are pesticides with several chemical compositions that are used with different aims. The aquatic environment has been considered the most relevant toxic receptor compartment, and so has attracted attention of researchers for evaluation of biological indicators. Thus, it becomes necessary to use methods of assessment of the effects of pollutants using fish to show the first signs of environmental stress caused by contaminants in different levels of biological organization. The morphological disorders in fish organs with wide surface area exposures to the environment, such as the gills, may be useful as biomarkers. The Thiodan® (Bayer), an insecticide and acaricide widely used to control chewing and sucking insects was chosen for this study. The use of small species, such as lambari Astyanax aff. bimaculatus, facilitates the execution of laboratory tests, reason for the choice of these species. This study determined the LC50-96h with 120 animals, divided in one as control group and seven concentrations of Thiodan® (1.5, 3, 6, 12, 24, 48 and 96 μg.L-1) with three replicates of five fish each. Also it has been evaluated the influence of Thiodan® on the morphology of the gills of female A. bimaculatus. The fish were distributed in four separate experiments (fish without adaptation and without food, fish without adaptation and fed, fish adapted and without food, and fish adapted and fed). For each experiment were used a control group and three concentrations of Thiodan® (1.3, 2.6 and 5.2 μg.L-1) lasting 96 hours, with three replicates of 10 fish in each aquarium. For morphological and morphometric studies, fragments of gills were processed following routine techniques. The water quality was measured and was according to the Resolution 357/2005 (CONAMA). The result of LC50-96h was 13.6μg.L-1 with a confidence interval from 10.1 to 18.4μg.L-1 (P<0.05). During the toxicity tests (96h) the exposed groups showed aggressive behavior and escape attempt in the highest concentration (5.2μg.L-1), restlessness, erratic swimming and branchial hyperventilation at all concentrations in four experiments. Histologically there was hyperplasia, lamellar fusion, detachment and destruction of the lamellar epithelium. The morphometric analysis showed a reduction of number and diameter of chloride cells, the thickness of the primary lamellae, and the length of the secondary lamellae, within and between experiments (P<0.05). It was observed an increase in the number of mucus cells and coincident points with the gill tissue (P<0.05) in the highest concentration (5.2μg.L-1) in experiments 1 and 2. There was an increase (P<0.05) in the diameter of the aneurysm in the experiment 1 when compared to the others. There was no difference (P>0.05) in the diameter of mucus cells, vasodilation, and the amount of the hemorrhage focus between the experiments. Morphometric analysis showed that changes in experiment 1 were more evident when compared to others. Based on these results the experiment showed that the gills of A. bimaculatus can be used as biomarkers of environmental contamination by Thiodan® but the fish should not be used as bioindicator organism, because it has low sensibility to this product. / Um dos fatores de maior relevância na poluição ambiental e que compromete um ecossistema é a contaminação por agrotóxicos, principalmente quando esses são aplicados de forma indiscriminada. Entre esses compostos estão pesticidas que possuem diferentes composições químicas e são utlizados com diversas finalidades. O ambiente aquático tem sido considerado o mais relevante compartimento receptor de tóxicos, e por isso tem despertado interesse de pesquisadores para avaliação de indicadores biológicos. Assim, torna-se necessário a aplicação de métodos de avaliação dos efeitos dos poluentes utilizando peixes para demonstrar os primeiros sinais de estresse ambiental causados por contaminantes em diferentes níveis de organização biológica. As alterações morfológicas dos órgãos de peixe com grande superfície de exposição ao meio ambiente, como as brânquias, podem ser úteis como biomarcadores. O Thiodan® (Bayer), um inseticida e acaricida amplamente utilizado para o controle de insetos chupadores e mastigadores, que apresenta ação por contato e ingestão, foi escolhido para o presente estudo. O uso de espécies de pequeno porte, como o lambari Astyanax bimaculatus facilita a execução dos testes em laboratório, motivo da escolha da espécie. O presente trabalho determinou a CL50-96h e avaliou a influência do Thiodan® (Bayer) sobre a morfologia das brânquias de fêmeas da A. bimaculatus em maturação gonadal. Foram utilizadas 600 fêmeas de lambaris, divididas em cinco lotes, que permaneceram em sistema estático para determinação da CL50-96h e para o teste de toxicidade. O primeiro lote de 120 animais, utilizado para a determinação da CL50-96h, foi constituído de três repetições com cinco peixes cada para o grupo controle e para cada concentração de Thiodan® (1,5; 3,0; 6,0; 12,0; 24,0; 48,0 e 96,0 μg.L-1). Os demais lotes foram distribuídos em quatro experimentos distintos (peixe sem adaptação e sem alimentação, peixes sem adaptação e alimentados, peixes adaptados e sem alimentação, e peixes adaptados e alimentados). Para cada experimento, utilizou-se um grupo controle e três diferentes concentrações de Thiodan® (1,3; 2,6 e 5,2μg/L), com três repetições de 10 peixes cada, durante 96h. Para estudos morfológicos emorfométricos, fragmentos de brânquias foram processados seguindo técnicas de rotina. Os parâmetros indicadores da qualidade da água utilizada para a realização dos experimentos encontraram-se em conformidade com as condições exigidas pela Resolução 357/2005 (CONAMA) para cultivo e criação de peixes tropicais. A CL50-96h obtida foi de 13,6μg.L-1 com intervalo de confiança de 10,1 a 18,4μg.L-1 (P<0,05). Durante os testes de toxicidade (96h), os grupos expostos apresentaram comportamento agressivo e tentativa de fuga na maior concentração (5,2μg.L-1), agitação, nado errático e hiperventilação branquial em todas as concentrações nos quatro experimentos. Histologicamente observou-se hiperplasia, fusão lamelar, descolamento e destruição do epitélio lamelar. As análises morfométricas mostraram redução de número e diâmetro de células de cloreto, da espessura das lamelas primárias, e do comprimento das lamelas secundárias, entre e dentro dos experimentos (P<0,05). Também foi observado aumento do número de células de muco e dos pontos coincidentes com o tecido branquial (P<0,05) na maior concentração (5,2μg.L-1) nos experimentos 1 e 2. Houve aumento (P<0,05) no diâmetro de aneurisma no experimento 1 em relação aos demais. No diâmetro de células de muco, na vasodilatação e na quantificação de foco de hemorragia entre os experimentos não houve diferença (P>0,05). A análise morfométrica mostrou que as alterações no experimento 1 (animais sem adaptação e sem alimentação) foram mais evidentes quando comparadas aos demais. Com base nesses resultados, pode se concluir que as brânquias de A. bimaculatus podem ser utilizadas como biomarcadores de contaminação ambiental pelo Thiodan®.
|
18 |
The Serotonergic System as a Target for Neuroendocrine Disruption in the Brain of Goldfish (Carassius auratus)Mennigen, Jan A. January 2011 (has links)
Serotonin stimulates reproduction and inhibits feeding/growth in the neuroendocrine brain of goldfish. The objective of this thesis is to study the effects of selective serotonin
reuptake inhibitor pharmaceuticals (SSRIs) on these systems, as SSRIs, such as fluoxetine, are detected in effluent and bioconcentrate in the brain of wild fish. Genes of the serotonin system were cloned to identify molecular conservation, seasonal expression, and tissue distribution. The serotonin transporter, the target molecule of fluoxetine, was highly conserved and ubiquitously expressed in goldfish. Seasonal changes of hypothalamic gene expression of the serotonin transporter support a role in the seasonal modulation of both processes. Fluoxetine injection experiments were used to assess effects on reproductive endpoints and to identify molecular mechanisms in the neuroendocrine brain. Fluoxetine inhibited serum estradiol concentrations in female goldfish and decreased isotocin mRNA abundance in the hypothalamus and telencephalon. Isotocin injections stimulated circulating estradiol concentrations, providing a causal link. Evidence for an involvement of serotonin in isotocin regulation was investigated using immunocytochemistry and 5-HT1A receptor agonists and antagonists. A close proximity of
serotonin fibers and isotocin cell bodies and fibers was found in the telencephalon and pituitary,respectively. Injection of a 5-HT1A receptor antagonist inhibited isotocin mRNA expression in the telencephalon. Identified gene targets were investigated in waterborne fluoxetine exposures,including environmental concentrations. Waterborne fluoxetine led to a reduction in basal and pheromone-stimulated milt volume in male goldfish. Gene expression evidence indicated a central inhibitory effect of fluoxetine through the decrease in mRNA abundance of follicle-stimulating hormone in the pituitary and isotocin in the telencephalon. Feeding rate and weight decreased in fluoxetine-injected goldfish, indicating an anorexigenic effect. Fluoxetine induced changes in the gene expression of the feeding peptides neuropeptide Y, corticotropin-releasing factor, and cocaine- and amphetamine-regulated transcript-I in the hypothalamus and telencephalon. Waterborne exposure to fluoxetine validated the anorexigenic effect in goldfish and was correlated with increased expression of corticotropin-releasing factor mRNA, an anorectic peptide. The thesis provides evidence for disrupting effects of fluoxetine on neuroendocrine control of reproductive
function and feeding/growth in goldfish, partially at environmental concentrations. The thesis provides the framework for the investigation of existing aquatic contaminants which modulate the serotonin system.
|
19 |
An Investigation of Pulp Mill Effluents and Their Wood Feedstocks as Potential Neuroendocrine Disruptors of the Fish Reproductive AxisWaye, Andrew January 2015 (has links)
Common observations of reduced gonad size and spawning inhibition in wild and laboratory raised fish exposed to pulp mill effluents indicate that reproductive neuroendocrine signalling pathways may be upset. This thesis supported the neuroendocrine disruption of reproduction hypothesis by identifying potential disruptors and targets where these impacts may occur. A mechanistic study of the in vivo fathead minnow (FHM) spawning assay used by industry to assess effluent quality showed that ovulation, but not milt production, was impaired. This finding supported the hypothesis that the neuroendocrine cascade that triggers ovulation may be disrupted. I hypothesized that neuroactive constituents previously described in effluents were originating in wood feedstocks and neuroactive extracts of hardwood and conifer feedstocks were identified. Phytochemicals associated with effluents were neuroactive. Structurally similar phenolic phytochemicals showed monoamine oxidase (MAO) inhibition, and resin acid diterpenes displayed glutamic acid decarboxylase (GAD) inhibition. Inhibitors of these enzymes may have impacts on the control of reproduction since MAO metabolizes dopamine, an inhibitor of the neuroendocrine reproductive axis, while GAD synthesizes -aminobutyric acid (GABA), a stimulator of this axis. Bioassay-guided fractionations of effluents and wood feedstocks identified that medium polar extracts of primary- and secondary-treated effluents and balsam fir feedstock contained high GAD inhibitory activity. This activity was associated with chemically complex fractions rather than single active principles. Advanced metabolomic comparison of medium polar extracts of feedstock and treated effluent identified 15 common plant metabolites, demonstrating that phytochemicals entering the mill in wood are surviving pulp production and effluent treatment processes and may be responsible for observed GAD inhibition. Discriminant metabolomics analysis identified 4-acetylpyridine, a novel compound to be described in effluents, as well as two other tentatively identified compounds, as chemical markers of GAD inhibitory effluent fractions. Five tentatively identified chemical markers and (+)-lariciresinol were found in inhibitory balsam fir feedstock fractions. Neuroendocrine pathways that control reproduction in fish, such as dopamine and GABA pathways, are also important drug targets for the treatment of neurological disorders in mammals; therefore these results also have implications for the development of natural health products from phytochemicals and tree extracts common to Canadian forests. By using an interdisciplinary approach (phytochemistry, neuroendocrinology, ecotoxicology), I was able to explore the various implications of my research on the fields of natural health products chemistry and aquatic toxicology.
|
20 |
Nickel bioaccumulation as a predictor of toxicityLeonard, Erin M. 04 1900 (has links)
<p>Recently, the focus of metal toxicity has shifted from concentrations within the aqueous environment to bioaccumulation within the organism. In this regard, the Biotic Ligand Model (BLM) relates the binding of metal at specific toxic sites (“ligands”) to eventual toxicity, whereas the Tissue Residue Approach (TRA) relates metal burdens at whole body, tissue, or subcellular levels to eventual toxicity. However, much less is currently known regarding Ni in comparison to other metals. This thesis addresses this knowledge gap by evaluating the use of Ni bioaccumulation as a predictor of toxicity in a number of fish and invertebrate species; bioaccumulation endpoints examined included Michaelis-Menten uptake parameters (K<sub>d</sub>, B<sub>max</sub>), a BLM parameter (log K<sub>NIBL</sub> values) and critical body residues (CBR50 values)</p> <p>More sensitive species exhibited higher binding affinities and lower binding capacities for Ni. In invertebrates, a strong overall correlation was observed between log K<sub>NiBL</sub> values for whole organism binding and acute toxicity to the extent that measurement of toxicity was an acceptable alternative to measurement of binding affinity, and vice versa. However, in two teleosts, the same comparison showed that a Ni BLM built on bioaccumulation would be more protective than one built on toxicity. The results further validated a central concept of the BLM - that short term metal bioaccumulation is predictive of longer term toxicity. Acute (96-h) Ni bioaccumulation predicted chronic (15 or 30-day) mortality in both salt and fresh water. In the latter, acute (96-h) sub-cellular bioaccumulations of Ni in either biologically active (BAM) or biologically inactive metal pools (BIM) of one fish species (round goby) were also predictive of 30-d mortality. However, goby were more sensitive to Ni bioaccumulation in the BAM versus BIM fraction.</p> <p>This thesis advances the use of bioaccumulation as a predictor of Ni toxicity and may have implications for metal toxicity frameworks such as the BLM and TRA.</p> / Doctor of Philosophy (PhD)
|
Page generated in 0.0786 seconds