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

Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 15, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Raymond D. Semlitsch Vita. Includes bibliographical references.

No description available.

No description available.

South Africa is one of the countries with the largest mining operations in the world. Most of these mines make use of natural dams and rivers in their water supply, which often are being pumped back into the natural environment. The reticulated water pumped back into the system may contain high concentrations of dissolved chemicals, which may lead to the reduction of the endemic organisms. Many of the heavy metals mined in South Africa are highly toxic at very low concentrations, and it is therefore very important to do frequent analysis on the aquatic environment. The value of chemical analysis per se has become limiting, as chemical analysis supplies information on the levels of chemicals at a certain time, and the new trend is to incorporate biological monitoring into existing monitoring strategies. Heat shock proteins are classified as stress proteins and are primarily expressed under stressful conditions, therefore having the potential to be used as possible biomarkers. Cortisol, also a known stress hormone, has been suspected of suppressing the expression of heat shock proteins by replacing the heat shock protein on the glucocorticoid receptor. This leads to reduced levels of heat shock proteins in the organism through a negative feedback mechanism. However, before information on heat shock proteins and cortisol can be successfully incorporated into ecological risk assessment, an understanding of how cortisol influences heat shock protein levels after heavy metal exposure is needed. This study aims to determine what effect cortisol had on the production of a specific member of the Hsp70 class of heat shock proteins at different time intervals after exposure of Oreochromis mossambicus to various metals. Proteins were determination using the Bradford method, while protein separation was done using Sodium Dodecyl Sulphate-Polyacrylamide Gel Electrophoresis. Thereafter, separated proteins were subjected to Western blotting and immunoblotting in order to quantify the different Hsp70 family members in the hepatic tissue. Cortisol levels were determined using a commercially available Cortisol ELISA Test Kit. Hsp70 accumulation occurred in only two exposure groups, namely the cadmium and chromium exposure groups. Accumulation of Hsp70 demonstrated an increase in accumulation rates at the 24 hour time interval of the 10% cadmium exposure group, with accumulation remaining relatively constant in the 20% cadmium exposure group. Accumulation of Hsp70 occurred only at the 48 and 96 hour time intervals in the 10% chromium exposure group. The accumulation of Hsp76 and Hsp74 were observed to follow the same pattern throughout the 96 hour exposure. In the 10% exposure groups accumulation of both Hsp76 and Hsp74 indicated an increase in accumulation rates at the 72 hour of groups exposed to chromium and nickel, whereas the accumulation of Hsp76 and Hsp74 remains constant after exposure to cadmium. In the 20% cadmium exposure group, an increase in Hsp76 and Hsp74 accumulation was observed at the 24 hour time interval, whereby accumulation of Hsp76 and Hsp74 remains constant in both the chromium and nickel 20% exposure groups. Males accumulated higher levels of Hsp70 members than females in the cadmium and chromium exposure groups. In the 10% exposure groups the females accumulated higher levels of Hsp74, whereas the males accumulated higher levels of Hsp74 in the 20% exposure groups. Accumulation of Hsp76 proved to be higher in the females in all exposure groups, compared to the males. Cortisol concentrations remained constant throughout the 96 hour exposure period, with higher cortisol levels observed in the chromium exposure groups. Cortisol concentrations proved to increase at higher concentrations of metal exposure. Cortisol proved to have no significant effect on Hsp70 family member accumulation, except in the cadmium exposure group, where a negative regression was observed. Accumulation of the HSp70 member can be linked to possible metal specificity, due to the fact that Hsp70 accumulated in only two metal species (cadmium and chromium). However, the accumulation of Hsp76 and Hsp74 may possibly prove that the higher concentrations of specific metals leads to early accumulation of heat shock proteins. The higher accumulation levels of Hsp70 in males, compared to accumulation levels in females may be due to the greater need to discard damadged or denatured proteins, whereas higher Hsp74 and Hp76 accumulation levels in females, may be due to the higher levels of reproductive proteins present in females, compared to males. This study therefore concluded that cortisol may have no significant effect on the accumulation of the Hsp70 family members in the liver of fish. / Prof. J.H.J. Van Vuren

Digitized by Kansas Correctional Industries

Call number: LD2668 .T4 1978 G34 / Master of Science

Inhalation of gallium arsenide (GaAs) particulates represent a potential health hazard in the semiconductor industry. Our results showed that GaAs was soluble under a variety of in vitro conditions. Arsenic levels in phosphate buffer filtrates indicated 78% dissolution by 36 hours. The in vivo dissolution of GaAs was dependent upon particle size, time, and route of administration. Intratracheal (i.t.) instillation of GaAs particulates (10-100 mg/kg) to rats resulted in blood arsenic levels of 5-187 ppm at 14-28 days, depending upon particle size. Dissolution doubled as the mean volume particle diameter was halved. Oral administration of GaAs particulates (10-1000 mg/kg) resulted in blood arsenic levels of 3-18 ppm at 14 days. Gallium was not detected in blood at any dose level by any route of exposure. Indices of toxicity that correlated to GaAs exposure were decreased weight gain and porphyria. These effects were maximal at 100 mg/kg GaAs i.t. Uroporphyrin replaced coproporphyrin as the major urinary metabolite. GaAs (10-100 mg/kg i.t.) resulted in an increase in the lung:body weight ratio (136-228%) at 14-28 days, depending upon particle size. Lungs retained 14-42% of the dose as gallium or arsenic. The increase in lung wet weight was not primarily due to edema although pulmonary edema increased in magnitude as particle size decreased. Lung dry weight, DNA, protein, and lipid content were also elevated 14 days after 100 mg/kg GaAs i.t. (large fraction). At this time and dose, major pathological lesions were a thickening in the alveolar wall, pneumonocyte hyperplasia, and interstitial pneumonia. Gallium, as Ga₂O₃ (65 mg/kg), accounted for the increase in lung lipids. Arsenic, as As₂O₃ (17 mg/kg), was responsible for the remaining changes in lung composition observed with GaAs administration. As₂O₃, but not GaAs, resulted in acute fibrosis at 14 days. With 100 mg/kg GaAs i.t. (smaller fraction), proteinosis, edema, mild fibrosis, and increased reticulin formation were observed over 1-28 days in addition to lesions previously described for the larger fraction. These results showed that oral and i.t. GaAs resulted in systematic arsenic intoxication. Intoxication was proportional to in vivo dissolution which was dependent upon particle size. GaAs i.t. was relatively more toxic to rats than an equivalent oral dose. The finding that urinary uroporphyrin levels were greater than coproporphyrin levels may serve as a sensitive, pretoxic indicator of GaAs exposure.

published_or_final_version / abstract / Ecology and Biodiversity / Master / Master of Philosophy

Gallium arsenide (GaAs) elicited a pulmonary inflammatory response in a dose dependent manner following a single exposure. A significant influx of leukocytes (polymorphonuclear cells) was observed 24 hours after intratracheal instillation of rats and hamsters. This led to an increase in the lung/body weight ratios. An increase in pulmonary DNA and total protein accompanied these observations. Histology confirmed the presence of increased numbers of pulmonary alveolar macrophages (PAM) even 1 week after exposure to GaAs. The instillation of GaAs also appeared to produce an oxidative stress in the lung only when the animals were given the 100 mg/kg dose and not the 10 mg/kg dose. Increased glutathione peroxidase and nonprotein sulfhydryls and depletion of ascorbic acid were evidence for the oxidative stress produced in the lung. These effects were dependent on the influx of phagocytic leukocytes. Analysis of the bronchoalveolar lavage fluid (BALF) also confirmed the involvement of phagocytic leukocytes in the progression of the lesions. Acid phosphatase activities increased significantly above the control levels 24 hours after exposure. The elevation of soluble protein and alkaline phosphatase indicated that the type I pneumocyte-capillary endothelial cell interface was compromised and the type II cells were damaged, respectively. The histological evaluations confirmed this phenomenon. Alveolar wall thickening was quite characteristic of the GaAs exposure. GaAs stimulated PAM to produce the active oxygen species, superoxide anion (O₂⁻) and H₂O₂, following in vitro and in vivo exposure. The dissolution of GaAs did not produce and O₂⁻ or H₂O₂ without the presence of cells. The cytotoxicity of GaAs was comparable to other compounds that elicit collagen deposition, As₂O₃ and silica. The semiconductor properties and potential dissolution products of GaAs may both contribute to its toxicity to PAM. The differences seen in the pulmonary lesions of silica (fibrosis) and GaAs (resorption of deposited collagen) treated animals may be due to the persistence of the particles. GaAs may be cleared by dissolution and silica cannot.