The pyrrolizidine alkaloids (PAs) and ergot alkaloids are known natural toxicants found in livestock forage. These alkaloids contribute to large economic losses in livestock throughout the world. An understanding of the mechanisms of toxicity and development of better diagnostic tools for better management practices was investigated. Variability exists in the toxicity of PAs in ruminants where cattle are more susceptible and sheep are more resistant. The mechanism of PA resistance in sheep has been attributed to hepatic metabolism or rumen microbial degradation of PAs to non-toxic moieties. The hepatic metabolism of the PA senecionine was investigated in cattle and sheep liver microsomes. The level of a toxic pyrrole metabolite 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine pyrrole (DHP) formed in cattle and sheep were similar. However, the level of a non-toxic N-oxide metabolite was greater in sheep than in cattle. Cytochrome P450 and flavin monooxygenases (FMOs) responsible for PA oxidative metabolism were similar in both ruminant species. Therefore, hepatic metabolism of PAs is not solely responsible for resistance observed in sheep versus cattle. Ergot alkaloids present in endophyte-infected plants also cause toxicity in livestock. HPLC is the typical method used to quantify ergot alkaloid content; however, it is costly and time-consuming. An enzyme-linked immunosorbent assay (ELISA) developed with lysergol as the hapten was evaluated to ascertain its feasibility as an analytical tool for the ergot alkaloids found in forage plants. The ELISA detected the presence of lysergic acid but was not a reliable assay for the ergopeptine alkaloids such as ergovaline. The genetic divergence in mice previously selected into ergot alkaloid susceptible and resistant lines was studied after ten generations of relaxed selection. Physiologically no difference was seen between the susceptible and resistant line for average daily weight gain. However, hepatic metabolism of the ergot alkaloid ergotamine showed differences between genders and between animals on diets containing no ergot alkaloids or a high concentration of ergot alkaloids. Four major biotransformation products were identified as hydroxylated ergotamine isomers based on mass spectroscopic analysis. / Graduation date: 2003

Environmental contamination along roadways with lead from processed petroleum and automotive residues has been reported. Toxicity to the herbivores grazing these areas has not been well studied. Comparison of lead concentrations adjacent to roads in Kuwait and in Oregon, USA was studied. Soil samples were taken from three sites at three different distances from the highway (0, 3 and 10 meters) adjacent to King Fahad Highway in Kuwait and Interstate 5 (I-5), Highway 34 (H-34) and Highway 20 (H-20) in Oregon. Soil was analyzed for lead concentrations. The mean lead concentrations in soil samples along King Fahad Highway were significantly higher (p<0.05) than those along 1-5, H-34 and 14-20 in Oregon [4943.6 ppm (mg/kg) vs 129 ppm, 94.9 and 81.67 ppm respectively]. In a field trial animal toxicity studies were conducted on sheep grazing near roadway in Kuwait and also in a controlled barn studies. Fifty lambs ranging in age from 4 to 9 months and grazing on Kuwait pasture adjacent to the King Fahad Highway were tested for blood lead. Levels were determined by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). Blood lead levels of these lambs ranged from 0.05-1.00 ppm. Only 12% of the tested population exceeded the blood lead above 0.1 ppm (the high normal value). None demonstrated any clinical signs of lead toxicosis. In addition, a controlled feeding trial was conducted with sheep ingesting similar concentrations of lead as were found along the roadways. These sheep were observed for clinical, gross and histopathological changes. Using the intensive lamb production system common in Kuwait, twenty five lambs ranging in age from 2-10 months were orally fed 0, 2, 4, 8 and 16 mg lead acetate/kg body weight/day in a controlled study. Blood lead levels were tested in these lambs at time zero, week two, and then at monthly intervals until the 14th week. All lambs were slaughtered and necropsied with select tissues analyzed for lead concentrations. Levels of lead in the blood were directly related to the daily administrated lead acetate (P<0.05). Neither gender, age nor breed of the sire had any affect on blood lead levels except for the 14th week where blood lead levels of the young lambs significantly exceeded (P<0.05) those in the older lambs with mean values of 0.54 and 0.34 ppm respectively. In general, lead levels in all the tested tissues were directly related to the amount of the daily oral administration of lead acetate. Differences between the tissue levels of lead in the experimental and control lambs (N=25) were statistically significant (P<0.05) in liver, bone and kidney but were not significant in trachea, testis, brain, diaphragm, ovary, lung, muscle, rumen, aorta, spleen, tongue, eye, intestine, heart and esophagus. Lead accumulation was the highest in bone at the lower ingested lead concentrations, but was the highest in the kidney at higher lead dosages. Lead values were significantly greater (P<0.05) in the livers of female lambs compared to those of the male. Bone, liver and kidney of the young lambs had significantly higher (P<0.05) levels of lead than older lambs with means of 19.24, 7.31 and 54.54 compared to 6.34, 3.59 and 21.31 ppm respectively. Gross lesions were not found in any of the 25 necropsied lambs. Histopathological changes of intranuclear inclusion bodies were found in 100% of the kidneys in lambs administered 8 mg/Kg/day and above and in 50% of the livers of the lambs administered the same dosages. Thirty three per cent of lambs administered 2 and 4 mg/kg/day had intranuclear inclusion bodies in their kidney but not in the liver. The controls had no inclusion bodies in any of these matching tissues. No clinical signs of lead toxicosis were observed in any lambs during the 14 weeks of the experiment. The same lamb population was used to compare blood lead levels and the growth performance of lambs (feed intake, weight gain and feed conversion) in relation to different dosages of lead acetate. Although there was a tendency for lambs ingesting the two higher lead doses to eat less feed, gain less weight; and have a lower feed conversion ratio, these differences were not statistically significant (P>0.05). The conclusion of these studies reveal some concern. Levels of lead as found near the highways of Kuwait were high enough to cause elevated tissue lead concentrations, particularly in liver and kidney, of lambs grazing adjacent to these highways. These levels cause tissue abnormalities in lambs and could be hazardous to human health eating the internal organs of these lambs. / Graduation date: 2000

Cerium(IV) oxide (CeO2), ceria, is an active metal oxide used in solid oxide fuel cells and for the purification of exhaust gases in vehicle emissions control. Behind these technically important applications of ceria lies one overriding feature, namely ceria's exceptional reduction-oxidation properties. These are enabled by the duality of the cerium ion which easily toggles between Ce4+ and Ce3+. Here the cerium 4f electrons and oxygen vacancies (missing oxygen ions in the structure) are key players. In this thesis, the nature of ceria's f electrons and oxygen vacancies are in focus, and examined with theoretical calculations. It is shown that for single oxygen vacancies at ceria surfaces, the intimate coupling between geometrical structure and electron localisation gives a multitude of almost degenerate local energy mimima. With many vacancies, the situation becomes even more complex, and not even state-of-the-art quantum-mechanical calculations manage to predict the experimentally observed phenomenon of vacancy clustering. Instead, an alternative set of computer experiments managed to produce stable vacancy chains and trimers consistent with experimental findings from the literature and revealed a new general principle for surface vacancy clustering. The rich surface chemistry of ceria involves not only oxygen vacancies but also other active oxygen species such as superoxide ions (O2−). Experiments have shown that nanocrystalline ceria demonstrates an unusually large oxygen storage capacity (OSC) and an appreciable low-temperature redox activity, which have been ascribed to superoxide species. A mechanism explaining these phenomena is presented. The ceria surface is also known to interact with SOx molecules, which is relevant both in the context of sulfur poisoning of ceria-based catalysts and sulfur recovery from them. In this thesis, the sulfur species and key mechanisms involved are identified.

Thesis (doctoral)--Helsinki University of Technology, 2000. / Includes bibliographical references. Also available on the World Wide Web.

Thesis (Ph. D.)--Open University. BLDSC no. DX214362.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 118-130). Also available in electronic version. Access restricted to campus users.

Thesis (Ph. D.)--University of Missouri-Columbia, 2003. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.

Thesis (M.E.S.)--The Evergreen State College, 2008. / Title from title screen (viewed 2/25/2010). Includes bibliographical references (leaves 68-70).

Foodborne toxins include a variety of biologically produced toxins and process-induced toxicants. Among them, marine algal toxins in polluted seafood can induce serious harmful effects on human, while heat-induced toxicants remain in a wide range of food and chronically affect health. In this present study, several representative toxins from these two categories were selected and studied, they are, brevetoxins (PbTxs), saxitoxin (STX) and acrolein (ACR). During past decades, the molecular actions of these toxins have been well studied, however, their effects and mechanisms corresponding to their sublethal toxicity in vivo still need more investigation. Therefore, in our current study, we adopted medaka fish (Oryzias melastigma) and zebrafish (Danio rerio) as models to study the toxicological responses and pathways of these selected toxins at the molecular and cellular level. In the first part of study, the targeted organs of medaka fish, gills and brains, were studied in medaka fish after exposure to the sublethal level of PbTx-1, the most potent neurotic shellfish poisoning (NSP) toxin. Facilitated by the two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ ionization tandem time-of-flight mass spectrometry (MALDI TOF/TOF MS), proteins affected by PbTx-1 in these organs were identified, including myosin like proteins, aldose reductase, gelsolin and keratin. Collectively, the proteins altered after exposure suggested the altered calcium ion binding process, and dysfunction in cytoskeleton assembly and metabolism. After successfully applying the fish model and proteomic approaches in the NSP toxin study, we put emphasis on the developmental toxicity of foodborne toxins, as children are more sensitive and vulnerable to foodborne toxins. Among the marine algal toxins, paralytic shellfish poisoning (PSP) toxins are the commonest and most lethal ones with STX as the most potent PSP toxin. Therefore, we examined the developmental effects of STX using medaka model. By exposing medaka embryos from the early blastula stage onwards, which covered the main developmental stage of the central nervous system and somites, we found newly hatched medaka fish exhibit abnormal growth with longer body length and relatively smaller yolk sac size. High cell proliferation, neuron development, and metabolism were confirmed by whole-mount immunostaining and 2-DE. In summary, STX disturbs the normal growth of medaka embryos probably by affecting the metabolic rate in the exposed medaka embryos. Opposite to STX, after exposure to ACR, a pollutant that ubiquitously exists in food and environment, the zebrafish exhibited delayed development. ACR is a known glutathione (GSH) depleting factor and oxidative stress inducer. Apart from developmental retardance, increased reactive oxygen species (ROS) and inflammation were found in newly hatched zebrafish, suggesting the developmental delay may be partly related to the ACR-induced oxidative stress. In summary, findings from the present study highlighted the molecular responses and possible pathways of some selected foodborne toxins. Developmental effects and toxicity were also found after exposing to both the biologically produced toxin and the heat-produced toxicant. Our current study makes contributions to the knowledge on the hazardous effects of foodborne toxins in vivo, and provides useful information for the further study on the human health. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy