Thesis (Ph. D.) University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on July 31, 2007) Includes bibliographical references.

No description available.

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

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Tez (Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, İç Hastalıkları Anabilim Dalı, 2008. / Kaynakça var.

Thesis (M. Phil.)--University of Hong Kong, 2007. / Also available online.

Thesis (M. Phil.)--University of Hong Kong, 2007. / Title proper from title frame. Also available in printed format.

Orientador: Fabio Erminio Mingato / Banca: Daniel Nicodemo / Banca: Cecilio Soares Filho / Resumo: O fígado possui grande importância no organismo animal, pois realiza a biotransformação de substâncias exógenas (xenobióticos) e por esse motivo, o tecido hepático acaba sendo alvo potencial de substâncias tóxicas. A bixina, proveniente das sementes de urucum (Bixa orellana L.) é um antioxidante que pode contribuir para a proteção das células e tecidos contra os efeitos deletérios dos radicais livres e também possui efeitos farmacológicos como antiinflamatório, antibacteriano e antitumoral. No presente trabalho foi avaliado o efeito protetor da bixina sobre os danos hepáticos provocados pelo tetracloreto de carbono (CCl ) em ratos. Os animais foram divididos em quatro 4 grupos de seis animais cada. A dose de CCl4 (0,125 mL/kg de peso corporal) foi injetada por via intraperitoneal (i.p.) e a bixina (5,0 mg/kg de peso corporal) foi administrada por gavagem por 7 dias antes da injeção do CCl . Após a 4 eutanásia, o sangue de cada animal foi colhido e foram analisadas a atividade sérica das enzimas alanina aminotransferase (ALT) e aspartato aminotransferase (AST). O fígado foi removido e após a preparação do homogenato foi analisada a atividade da enzima glutationa redutase (GR), os níveis de glutationa reduzida (GSH) e nicotinamida adenina dinucleotídeo fosfato na forma reduzida (NADPH), além da peroxidação dos lipídios de membrana e alterações histopatológicas. A bixina protegeu os danos hepáticos provocados pelo CCl4 conforme observado pela diminuição da liberação das enzimas ALT e AST. A bixina também protegeu o fígado contra os efeitos oxidantes do CCl , uma vez que impediu a diminuição da atividade da enzima 4 GR e dos níveis de GSH e NADPH. A peroxidação dos lipídios de membrana também foi inibida pela bixina. Além disso, o dano histopatológico do fígado foi significativamente reduzido pelo... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract:The liver has a great importance in the animal body since it is responsible to the biotransformation of exogenous chemicals (xenobiotics), making the liver tissue a potential target for toxic substances. The carotenoid bixin from annatto seeds (Bixa orellana L.) is an antioxidant that can contribute to protecting cells and tissues against the deleterious effects of free radicals and also has pharmacological effects such as anti-inflammatory, antibacterial and antitumoral activities. In the present study we evaluated the protective effect of the bixin on liver damage caused by carbon tetrachloride (CCl ) in rats. 4 The animals were divided in four groups of six rats in each. The dose of CCl4 (0.125 mL kg-1 body wt.) was injected i.p. and bixin (5.0 mg kg-1 body wt.) was given by gavage 7 days before the CCl4 injection. After euthanasia, the blood of each animal was collected and the serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. The livers were removed and after preparation of the homogenate the activity of the enzyme glutathione reductase (GR), the levels of reduced glutathione (GSH) and NADPH, as well as the peroxidation of membrane lipids and histopathological changes were determined. Bixin reduced the liver damage caused by CCl4 as noted by the significant decrease of the release of the enzymes ALT and AST. Bixin also protected the liver against the oxidizing effects of CCl , since it 4 prevented the decrease in GR activity and levels of GSH and NADPH. The peroxidation of membrane lipids was also inhibited by bixin. Moreover, the histopathological damage of liver was also significantly reduced by bixin treatment. Therefore, we can conclude that the protective effect of bixin against... (Complete abstract click electronic access below) / Mestre

Made available in DSpace on 2014-06-11T19:30:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-11-12Bitstream added on 2014-06-13T19:39:55Z : No. of bitstreams: 1 moreira_pr_me_araca.pdf: 315047 bytes, checksum: 1a5a979a465e9cd8dca5be26006d8106 (MD5) / O fígado possui grande importância no organismo animal, pois realiza a biotransformação de substâncias exógenas (xenobióticos) e por esse motivo, o tecido hepático acaba sendo alvo potencial de substâncias tóxicas. A bixina, proveniente das sementes de urucum (Bixa orellana L.) é um antioxidante que pode contribuir para a proteção das células e tecidos contra os efeitos deletérios dos radicais livres e também possui efeitos farmacológicos como antiinflamatório, antibacteriano e antitumoral. No presente trabalho foi avaliado o efeito protetor da bixina sobre os danos hepáticos provocados pelo tetracloreto de carbono (CCl ) em ratos. Os animais foram divididos em quatro 4 grupos de seis animais cada. A dose de CCl4 (0,125 mL/kg de peso corporal) foi injetada por via intraperitoneal (i.p.) e a bixina (5,0 mg/kg de peso corporal) foi administrada por gavagem por 7 dias antes da injeção do CCl . Após a 4 eutanásia, o sangue de cada animal foi colhido e foram analisadas a atividade sérica das enzimas alanina aminotransferase (ALT) e aspartato aminotransferase (AST). O fígado foi removido e após a preparação do homogenato foi analisada a atividade da enzima glutationa redutase (GR), os níveis de glutationa reduzida (GSH) e nicotinamida adenina dinucleotídeo fosfato na forma reduzida (NADPH), além da peroxidação dos lipídios de membrana e alterações histopatológicas. A bixina protegeu os danos hepáticos provocados pelo CCl4 conforme observado pela diminuição da liberação das enzimas ALT e AST. A bixina também protegeu o fígado contra os efeitos oxidantes do CCl , uma vez que impediu a diminuição da atividade da enzima 4 GR e dos níveis de GSH e NADPH. A peroxidação dos lipídios de membrana também foi inibida pela bixina. Além disso, o dano histopatológico do fígado foi significativamente reduzido pelo... / The liver has a great importance in the animal body since it is responsible to the biotransformation of exogenous chemicals (xenobiotics), making the liver tissue a potential target for toxic substances. The carotenoid bixin from annatto seeds (Bixa orellana L.) is an antioxidant that can contribute to protecting cells and tissues against the deleterious effects of free radicals and also has pharmacological effects such as anti-inflammatory, antibacterial and antitumoral activities. In the present study we evaluated the protective effect of the bixin on liver damage caused by carbon tetrachloride (CCl ) in rats. 4 The animals were divided in four groups of six rats in each. The dose of CCl4 (0.125 mL kg-1 body wt.) was injected i.p. and bixin (5.0 mg kg-1 body wt.) was given by gavage 7 days before the CCl4 injection. After euthanasia, the blood of each animal was collected and the serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. The livers were removed and after preparation of the homogenate the activity of the enzyme glutathione reductase (GR), the levels of reduced glutathione (GSH) and NADPH, as well as the peroxidation of membrane lipids and histopathological changes were determined. Bixin reduced the liver damage caused by CCl4 as noted by the significant decrease of the release of the enzymes ALT and AST. Bixin also protected the liver against the oxidizing effects of CCl , since it 4 prevented the decrease in GR activity and levels of GSH and NADPH. The peroxidation of membrane lipids was also inhibited by bixin. Moreover, the histopathological damage of liver was also significantly reduced by bixin treatment. Therefore, we can conclude that the protective effect of bixin against... (Complete abstract click electronic access below)

published_or_final_version / abstract / Chinese Medicine / Master / Master of Philosophy