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Investigation of the Toxicity and Toxicokinetics of Selenium from the Accumulator Plant Symphyotrichum spathulatum (Western Mountain Aster) in SheepWilhelm, Amanda 01 May 2010 (has links)
This study was designed to observe the effects of selenium from plant material in sheep after a single, oral dose. Purified sodium selenite and selenomethionine were given as positive controls. The plant Symphyotrichum spathulatum (Western Mountain Aster) was collected, analyzed for selenium content, and administered orally to sheep at varying doses according to body weight. Clinical signs were observed for 7 days during which time whole blood, serum, and expired air were collected. Following euthanasia, tissues were collected for histopathological analysis and mineral analysis. Clinical signs were less apparent than expected and included depression and mild dyspnea in sheep receiving the highest doses of selenium as plant material, whereas pathologic lesions were prominent. Acute myocardial degeneration and necrosis was most severe in the highest dose animals, but present to lesser degrees as dose decreased. Pulmonary lesions of edema and congestion were less frequently observed. Thirteen animals died prior to study completion. Selenium concentration in tissues, brain, liver, kidney cortex, atrium, ventricle, and skeletal muscle, increased with increasing dose of plant material. Treatment had a significant impact on selenium concentration in all tissues collected for mineral analysis (P < 0.01). Whole blood and serum were collected to study the toxicokinetics of selenium in these sheep. Serum kinetic parameters that increased significantly with increasing dose included the elimination rate constant, peak selenium concentration, and area under the selenium concentration versus time curve. Serum kinetic parameters that significantly decreased with increasing dose included the absorption and elimination half-lives. Whole blood kinetic parameters that increased significantly with increasing dose included the elimination rate constant, peak selenium concentration, and area under the curve. Expired air was collected to study the respiratory toxicokinetics of selenium in the sheep. The selenium concentration in expired air from sheep receiving selenomethionine was significantly greater than all other treatments (P < 0.0001) at all collection time points. But an intriguing finding was the dramatic differences in elimination profile curves as selenium dose increased with the plant material. The highest dose group elimination curve continually increased through all collection time points. All other groups dosed with plant material saw a decrease in selenium elimination by the last collection time point.
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