Graduate Thesis Or Dissertation
 

Senecio jacobaea : toxicity and effects on mineral metabolism in animals

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  • Several experiments were conducted to examine the toxicity of Senecio jacobaea (SJ) in animals resistant to pyrrolizidine alkaloid (PA) intoxication and to determine the extent of alterations in mineral metabolism as a result of SJ intoxication. Inclusion of SJ into diets containing added copper (Cu) resulted in increased (P<.01) liver Cu levels when fed to rats. Percent distribution of total Cu in intracellular fractions was increased in the nuclei and debris (P<.001) and decreased in the lysosomes and cytosol (P<.05) as a result of dietary SJ. Elevated spleen weights (P<.001), and serum ceruloplasmin activity (P<.01) were also observed in rats fed SJ. Results suggest an impairment or saturation of hepatic intracellular excretory mechanisms for Cu during SJ intoxication. Guinea pigs were determined to be extremely resistant to dietary SJ and injected monocrotaline, but susceptible to injected Senecio alkaloids. The chronic lethal dose (LD₁₀₀) of SJ for guinea pigs was 525% of initial body weight. Histopathology of liver tissue revealed extensive megalocytosis, cytoplasmic and nuclear vacuolization, biliary hyperplasia and periportal fibrosis. Centrilobular areas appeared spared from necrotic lesions. An increase (P<.05) in liver Cu levels was observed in SJ fed rabbits. Results suggest this increase was not due to PA induced changes in gastrointestinal (GIT) absorption of minerals. PA were found to be readily transferred across the GIT of rabbits in vivo and in vitro. These results suggest the resistance of rabbits to dietary SJ intoxication may be due to efficient urinary elimination of PA and(or) metabolites but not low PA absorption across the GIT. Accumulation of liver Cu in sheep fed SJ only occurred when hepatic microsomal mixed function oxidases (MFO) were induced by phenobarbital. Microsomal epoxide hydrolase activity was found to be high in normal sheep when compared to previously reported values for rats. Histopathology of liver tissue from sheep fed SJ indicated periportal but not centrilobular lesions. Results suggest that MFO induction does not increase the sensitivity of sheep to SJ intoxication. Chromatographic analysis of sheep rumen fluid-SJ incubation mixtures indicated an overall release of PA from plant material, without formation of the non-toxic metabolite, 7Q-0H-1-methylene &apyrrolizidine. In addition, SJ fermented in sheep rumen fluid retained its toxicity to rats.
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Déclaration de droits
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  • File scanned at 300 ppi (Monochrome, 256 Grayscale) using Capture Perfect 3.0.82 on a Canon DR-9080C in PDF format. CVista PdfCompressor 4.0 was used for pdf compression and textual OCR.
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