Tanto no Brasil como em vários outros países, a Senna occidentalis é uma planta de interesse agropecuário, pois é encontrada em pastos ou como contaminante de cereais, podendo, causar intoxicação na criação animal. Além disto, vem sendo utilizada, empiricamente, na Medicina Humana, para o tratamento de várias afecções. Em estudo recente, verificou-se que frangos tratados com sementes de S. occidentalis apresentavam, além das lesões musculares, alterações em órgãos linfóides. Assim, o presente trabalho procurou verificar se as sementes de S. occidentalis poderiam produzir efeitos tóxicos nos órgãos linfóides de mamíferos, utilizando, para tal, ratos como modelo experimental. As sementes de S. occidentalis foram administradas, durante 14 dias, a ratos Wistar (150-200g), em diferentes concentrações de sementes desta planta na ração: 1% (So1), 2% (So2) e 4%(So4). Os animais do grupo peer-feeding (PF) receberam a mesma quantidade de ração consumida pelos animais tratados com So4, porém isentas da planta. Foram avaliados os seguintes parâmetros: consumo de água e ração e ganho de peso, avaliação hematológica e bioquímica, além da histopatologia, morfometria e de ensaios preconizados para o estudo da resposta imunológica não específica. Todos os ratos pertencentes aos diferentes grupos experimentais apresentaram diminuição no consumo de ração e água e no ganho de peso. A avaliação hematológica revelou anemia microcítica e hipocrômica nos animais que receberam 4% da planta. Além disso, todos os animais dos grupos So2 e So4 apresentaram depleção de células linfóides e redução da polpa branca do baço. Os ratos pertencentes ao grupo So4 apresentaram redução significante no peso relativo do timo e diminuição significante na região cortical e também no diâmetro dos folículos medulares deste órgão. Estes mesmos animais apresentaram diminuição da produção de água oxigenada e óxido nítrico. Em relação à resposta inflamatória, todos os animais dos grupos experimentais, apresentaram redução na evolução do edema inflamatório agudo e crônico. Assim, a presente pesquisa mostrou que, também em mamíferos, a S. occidentalis pode comprometer o sistema imunológico, haja vista as alterações encontradas no timo e baço dos ratos expostos à planta. Além disso, verificou-se que as sementes desta planta também promovem efeitos tóxicos sobre eritrócitos e alterações na resposta inflamatória. A inclusão do grupo PF permitiu verificar que os efeitos aqui encontrados não são devidos a possíveis alterações nutricionais promovidas pela queda do consumo de alimento e sim relacionados ao efeito tóxico direto da S. occidentalis. / Senna occidentalis is a weed which grows in pasture along fences and fields cultivated with cereals as corn and soybean and many reports have been showing intoxication with this plant in different animal species. The effects of daily administration of S. occidentalis seeds in different concentrations 1% (So1), 2 % (So2) and 4% (So4) in ration was investigated in rats. It was also evaluated the effects of rats that received the same amount of ration to those of So4-group, however free of S. occidentalis seeds, (PF-rats). The experimental period lasted 14 days and the effects were evaluated on the basis of food consumption, weight gain, hematological and biochemical parameters, inflammatory and immunological responses, as well as histopathology, relative organ weight and morphometric analysis. All experimental animals, showed significant decrease in ration and water consumption and body weight gain. The hematological parameters revealed microcytic and hypochromic anemia in those animals treated with the higher concentration S. occidentalis seeds. Morphometric analysis of the spleen from So2 and So4-animals displayed a significant decrease in the cortical thickness. The thymus from So4-rats showed reduction in the organ size, and the morphometry revealed thickness and reduction of the diameter of the follicles at the cortical area. The same animals presented reduction in hydrogen peroxide and nitric oxide production. In inflammatory response all experimental animals, showed significant decrease in the evolution of acute and chronic edema. These results showed that the alterations found in this present study are related to the poisonous effects of the S. occidentalis and not to the malnutrition.

O objetivo do presente estudo foi avaliar os efeitos tóxicos da Senna occidentalis (So) sobre o sistema linfo-hematopoiético em ratos recém-desmamados ou expostos pré-natalmente. Avaliou-se nestes animais: o consumo de água e ração, o ganho de peso; parâmetros hematológicos, padrões histopatológicos, além da resposta imunológica específica e não específica. Inicialmente, o estudo foi realizado em ratos recém-desmamados, os quais foram expostos a diferentes concentrações de sementes de So na ração a saber: 1% (So1), 2% (So2) e 4% (So4) durante 14 dias ou que receberam So4 durante 28 dias. Os animais do grupo peer-feeding (PF) receberam a mesma quantidade de ração consumida pelos animais expostos a So4, porém isentas da planta. Após 14 dias de exposição, os resultados obtidos mostraram uma diminuição significante nos parâmetros de consumo de ração, de ganho de peso e da celularidade da medula óssea e do peso relativo no timo nos grupos So2 e So4 e um aumento no peso relativo do baço nos grupos So2 e So4. Entretanto, os animais dos grupos So4 e PF também apresentaram diminuição da celularidade da medula óssea. Na avaliação da resposta imune não especifica todos grupos expostos às sementes da planta, bem como o grupo PF, apresentaram redução na porcentagem de fagocitose por neutrófilos; porém, apenas o grupo So4 mostrou redução do burst basal por neutrófilos. O estudo morfológico do baço mostrou proliferação hematopoiética extramedular e aumento de megacariócitos multinucleados nos ratos do grupo So4. Apenas nos experimentos com animais do grupo So4 expostos por 28 dias, verificou-se similaridade entre resultados dos parâmetros acima descritos, além da ocorrência de anemia microcítica e hipocrômica. Num segundo momento avaliou-se as proles de ratas que receberam sementes de S. occidentalis a 4% na ração, do 6º ao 20º dia de gestação, assim como as proles das ratas do grupo peer-feeding (PF). Os filhotes provenientes de mães do grupo So4 e PF apresentaram um aumento do burst oxidativo e da fagocitose por neutrófilos. Os animais da prole do grupo PF apresentaram hemograma indicativo de anemia megaloblástica. Já no estudo morfológico do baço verificou-se hematopoiese extramedular nos filhotes das mães do grupo So4. Portanto, a presente pesquisa mostrou que a S. occidentalis pode comprometer alguns parâmetros do sistema imunológico de ratos expostos às sementes da planta durantes diferentes fases do desenvolvimento. Além disso, verificou-se que as sementes desta planta também promovem efeitos tóxicos sobre eritrócitos. A inclusão do grupo PF permitiu verificar que os efeitos observados não são decorrentes de possíveis alterações nutricionais promovidas pela redução do consumo de ração, mas sim relacionados ao efeito tóxico direto da S. occidentalis. / The aim of present study was to determinate the Senna occidentalis (So) toxic effects on lymphohematopoetic system in rats during the growth and pre-natal period. The effects were evaluated on the basis of food consumption, weight gain, hematological and immunological parameters, as well as histopathology analysis. Initially, the study was done in growing rats exposed to S. occidentalis seeds in different concentrations: 1% (So1), 2% (So2) and 4% (So4) in feed during 14 or 28 days. Peer feeding-group of rats (PF) was also evaluated; this group received the same amount of feed of those from So4-group, however, free of S. occidentalis seeds. S. occidentalis 14 days exposure decreased food consumption, weight gain, thymus relative organ weight and bone marrow cellularity and increased the spleen relative weight of rats from So2 and So4-group. However, So4- and PF- groups also presented a decreased bone marrow cellularity. All seed exposed-groups and also PF-group had a decrease on neutrophil phagocytosis percentage; however, only rats from So4-group had a decreased neutrophil basal burst. Spleen morphologic analysis indicated the presence of extramedular hematopoietic proliferation and increased multinucleated megakariocytes on So4-group. Similar results were found for all the parameters described after S. occidentalis exposure during 28 days. Furthermore, the rats of So-4 group presented microcytic and hypochromic anemia. On a second moment, rats offspring exposed to S. occidentalis at 4% in feed during the 6th to 20th gestational day and rats offspring of PF group were evaluated. The So4- and PF- rats offspring groups presented an increased neutrophil oxidative burst and phagocytosis, however PF-rats offspring group also had an altered complete blood count compatible with megaloblastic anemia. Moreover spleen morphologic analysis indicated the presence of extramedular hematopoiesis on So4 rats offspring group. Therefore, the present study showed that S. occidentalis can compromise some immunological parameters in rats exposed to seeds during different development periods. This exposure also promotes toxic effects on erythrocytes. The PF group allowed us to verify that the observed effects are related to direct S. occidentalis toxic effects and not due a possible nutritional alteration caused by the reduced feed ingestion.

Made available in DSpace on 2016-08-15T20:31:37Z (GMT). No. of bitstreams: 1 MairaCJSL_DISSERT.pdf: 420836 bytes, checksum: 822f4cc895779b5cc7c308d8152a664d (MD5) Previous issue date: 2011-02-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study aimed to evaluate the spontaneous cases of poisoning in goats, rats and toxicity in vitro cytotoxicity of Aspidospema pyrifolium. In all spontaneous cases studied, the plant is ingested and the abortion cases occurred exclusively in goats. Most cases of abortion occurred during the dry season and early rainy season, and experienced the goats were less affected than the young goats. We used male and female rats of Wistar strain. The extract of the plant A. pyrifolium was administered in females at day 15 of gestation or from the 15th to the 17th day of gestation, which showed reduced fetal weight and strong evidence of maternal toxicity. Rats subjected to intraperitoneal injection of the extract of A. pyrifolium showed motor dysfunction and death, male rats were more resistant than females. The administration of atropine, diazepam and xylazine did not help in preventing the effects of toxicity. The evaluation of osmotic fragility of red blood cells was performed with the plant extract in different concentrations. In addition, we used larvae from a day of brine shrimp, which were incubated with different concentrations of the extract. It was found that the extract of A. pyrifolium promoted hemolysis and was lethal to A. saline. These in vitro tests may be useful as adjunct tests for further studies with this plant. / O presente trabalho teve por objetivo avaliar casos espontâneos de intoxicação em caprinos, toxicidade em ratos e citotoxicidade in vitro da Aspidospema pyrifolium. Em todos os casos espontâneos estudados, a ingestão da planta e os casos de aborto ocorreram exclusivamente em caprinos. A maioria dos casos de aborto ocorreu durante a estação seca e início da estação chuvosa, e as cabras experientes eram menos afetadas do que as cabras jovens. Foram utilizados ratos machos e fêmeas da linhagem Wistar. O extrato obtido da planta A. pyrifolium foi administrado nas fêmeas no 15º dia de gestação ou a partir do 15º ao 17º dia de gestação, que apresentaram redução do peso fetal e fortes indícios de toxicidade materna. Ratas submetidas a injeção intraperitoneal do extrato da A. pyrifolium apresentaram distúrbios motores e morte; ratos machos foram mais resistentes do que as fêmeas. A administração de atropina, xilazina e diazepam não auxiliou na prevenção dos efeitos de toxicidade. A avaliação da fragilidade osmótica das células vermelhas do sangue foi realizada com o extrato da planta em diferentes concentrações. Além disso, utilizou-se larva de um dia de Artemia salina, que foram incubadas com diferentes concentrações do extrato. Verificou-se que o extrato de A. pyrifolium promoveu hemólise e foi letal para A. salina. Estes testes in vitro podem ser úteis como testes adjuntos de mais estudos com esta planta.

Made available in DSpace on 2014-06-11T19:25:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-12-15Bitstream added on 2014-06-13T18:29:08Z : No. of bitstreams: 1 garcia_af_me_araca.pdf: 1332928 bytes, checksum: d6b709a9f4bbd3e7b0f6b54781c3026a (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Lantana camara (Verbenaceae) é uma importante planta daninha tropical que causa hepatotoxicidade tanto em ruminantes como em humanos. A maioria dos compostos isolados das folhas da lantana são triterpenóides pentacíclicos conhecidos como lantadenos, sendo o mais abundante o lantadeno A (LA). As mitocôndrias desempenham uma função crucial na manutenção dos processos celulares dependentes de ATP. Neste trabalho foi avaliada a ação do LA e do seu metabólito reduzido (RLA) na bioenergética estudando os seus efeitos na respiração, potencial de membrana e níveis de ATP em mitocôndrias isoladas de fígado de rato energizadas com succinato. Na faixa de concentração testada (5–25 µM), RLA estimulou a respiração de estado 4 e inibiu a de estado 3, estimulou a respiração de estado 3 inibida pela oligomicina, dissipou o potencial de membrana e diminuiu os níveis de ATP de uma forma dose-dependente. Entretanto, LA não estimulou a respiração de estado 4, nem afetou os outros parâmetros mitocondriais na mesma extensão que o RLA. Os lantadenos não inibiram a respiração desacoplada por CCCP, mas estimularam a atividade da ATPase em mitocôndrias intactas acopladas. A atividade da ATPase em mitocôndrias intactas desacopladas ou rompidas não foi afetada pelos compostos. Portanto, RLA age como um desacoplador da fosforilação oxidativa e o LA age em outros componentes da membrana mitocondrial que não a ATP sintase afetando a bioenergética mitocondrial. Esses efeitos podem contribuir para a hepatotoxicidade da lantana. / Lantana camara (Verbenaceae) is an important tropical weed that causes hepatotoxicity even in ruminant or in human. The principal isolated compounds of lantana are the pentacyclic triterpenoids known as lantadenes, being the lantadene A (LA) the most abundant. Mitochondria are key to the maintenance of many cellular functions dependent of ATP. This work addressed the action of LA and its reduced derivative (RLA) on mitochondrial bioenergetics by assessing their effects on respiration, membrane potential and ATP levels in succinate-energized isolated rat liver mitochondria. At the concentration range tested (5–25 µM), RLA stimulated state-4 respiration, inhibited state-3 respiration, circumvented oligomycin-inhibited state-3 respiration, dissipated membrane potential and depleted ATP in a dose-dependent manner. However, LA did not stimulate state-4 respiration, nor did it affect the other mitochondrial parameters to the extent of its reduced derivative. The lantadenes didn’t inhibit the CCCP-uncoupled respiration but increased the ATPase activity of intact coupled mitochondria. The ATPase activity of intact uncoupled or disrupted mitochondria was not affected by the compounds. Therefore, RLA acts as a mitochondrial uncoupler of oxidative phosphorylation and LA acts in other mitochondrial membrane components rather than the ATP synthase affecting the mitochondrial bioenergetics. Such effects may account for the hepatoxicity of lantana.

Orientador: Fábio Erminio Mingatto / Banca: Daniel Junqueira Dorta / Banca: Sérgio Diniz Garcia / Resumo: Lantana camara (Verbenaceae) é uma importante planta daninha tropical que causa hepatotoxicidade tanto em ruminantes como em humanos. A maioria dos compostos isolados das folhas da lantana são triterpenóides pentacíclicos conhecidos como lantadenos, sendo o mais abundante o lantadeno A (LA). As mitocôndrias desempenham uma função crucial na manutenção dos processos celulares dependentes de ATP. Neste trabalho foi avaliada a ação do LA e do seu metabólito reduzido (RLA) na bioenergética estudando os seus efeitos na respiração, potencial de membrana e níveis de ATP em mitocôndrias isoladas de fígado de rato energizadas com succinato. Na faixa de concentração testada (5-25 µM), RLA estimulou a respiração de estado 4 e inibiu a de estado 3, estimulou a respiração de estado 3 inibida pela oligomicina, dissipou o potencial de membrana e diminuiu os níveis de ATP de uma forma dose-dependente. Entretanto, LA não estimulou a respiração de estado 4, nem afetou os outros parâmetros mitocondriais na mesma extensão que o RLA. Os lantadenos não inibiram a respiração desacoplada por CCCP, mas estimularam a atividade da ATPase em mitocôndrias intactas acopladas. A atividade da ATPase em mitocôndrias intactas desacopladas ou rompidas não foi afetada pelos compostos. Portanto, RLA age como um desacoplador da fosforilação oxidativa e o LA age em outros componentes da membrana mitocondrial que não a ATP sintase afetando a bioenergética mitocondrial. Esses efeitos podem contribuir para a hepatotoxicidade da lantana. / Abstract: Lantana camara (Verbenaceae) is an important tropical weed that causes hepatotoxicity even in ruminant or in human. The principal isolated compounds of lantana are the pentacyclic triterpenoids known as lantadenes, being the lantadene A (LA) the most abundant. Mitochondria are key to the maintenance of many cellular functions dependent of ATP. This work addressed the action of LA and its reduced derivative (RLA) on mitochondrial bioenergetics by assessing their effects on respiration, membrane potential and ATP levels in succinate-energized isolated rat liver mitochondria. At the concentration range tested (5-25 µM), RLA stimulated state-4 respiration, inhibited state-3 respiration, circumvented oligomycin-inhibited state-3 respiration, dissipated membrane potential and depleted ATP in a dose-dependent manner. However, LA did not stimulate state-4 respiration, nor did it affect the other mitochondrial parameters to the extent of its reduced derivative. The lantadenes didn't inhibit the CCCP-uncoupled respiration but increased the ATPase activity of intact coupled mitochondria. The ATPase activity of intact uncoupled or disrupted mitochondria was not affected by the compounds. Therefore, RLA acts as a mitochondrial uncoupler of oxidative phosphorylation and LA acts in other mitochondrial membrane components rather than the ATP synthase affecting the mitochondrial bioenergetics. Such effects may account for the hepatoxicity of lantana. / Mestre

The Forensic Chemistry Laboratory of Johannesburg (FCL JHB) is tasked with the chemical analysis of a variety of samples to assist in determining the cause of death where unnatural cause is suspected. Some of the samples submitted to the laboratory have a herbal or muti connotation, but a large portion of these cases turn out to have no herbal components present as only pharmaceutical or agricultural products are detected in these samples. This study combined, for the first time, forensic investigation, chemistry and botany to create a unique platform needed for the identification of poisonous plants and their components in forensic exhibits and viscera. The research was focussed on the poisonous plants previously detected at the laboratory, as well as the requests received for the analysis of muti/toxic plant components. The selection of plants included Nicotiana glauca, Datura stramonium / Datura ferox, Callilepis laureola, Boophone disticha / Ammocharis coranica, Abrus precatorius, Ricinus communis, Nerium oleander / Thevetia peruviana and Bowiea volubilis. All these species are known to have caused fatalities, hence their choice. Nicotiana glauca has been implicated in the deaths of at least 15 people since 2001. It was previously detected by GC-MS (EI) in plant exhibits, but could not be detected in a viscera matrix. A selective extraction method for alkaloids was used to extract botanical and viscera samples. Anabasine was successfully detected on the HPLC-MS (EI) system but this detection technique was not considered sensitive enough. A very sensitive HPLC-MS method was developed on the ZMD detector by using electrospray technology. This method outperformed both electron impact detectors (GC and HPLC) and could detect 1ng/ml anabasine with relative ease in full scan mode. Datura stramonium and D. ferox have not been previously positively linked to any human poisoning or death due to exposure to botanically derived products at the FCL JHB. Atropine and scopolamine were successfully ionised in ESI positive mode and could be detected at 10 pg/ml and 100 pg/ml level respectively. The identities of the compounds were confirmed by characteristic ISCID fragmentation patterns. The developed method was successfully applied to a suspected heart attack case. The results proved conclusively that the deceased was given D. ferox seeds as part of his meal and an overdose of atropine and scopolamine contributed to his death. Callilepis laureola is reputed to be one of the more commonly used medicinal plants in South Africa, and although its use has been indicated by the specific mention of a possible nephrotoxin and/or hepatotoxin as causative agent, it has not been detected in any of the forensic chemistry laboratories in South Africa. This was mainly due to the absence of a reliable method for the analysis of the main toxic component of C. laureola, atractyloside, by mass spectrometry. A sensitive and very selective HPLC-ESI-MS method was developed that could detect atractyloside, carboxyatractyloside and their monodesulfated analogues in botanical and viscera matrices. The method was successfully applied to a variety of forensic samples and proved that C. laureola may play an important role in herbal poisonings. In a selection of suspected herbal poisonings where the cause of poisoning was unknown, 30% of the samples tested positive for the presence of atractyloside, carboxyatractyloside or their monodesulfated analogues. The bulbs of Boophone disticha are rich in isoquinoline alkaloids and some of the alkaloids were detected by GC-EI-MS and LC-EI-MS, but the detection of these alkaloids in viscera samples was not successful. A routine method used for the screening for drugs of abuse in forensic samples, were successfully used for the analysis of the bulb extracts of B. disticha and the bulb scales of A. coranica. The chromatographic profile of these two plants appeared very similar at a first glance, but a closer evaluation of the mass spectra highlighted significant differences between the two plants. Six alkaloids from B. disticha were isolated and characterised by LC-MS and NMR and these compounds were detected in suspected herbal poisoning cases. It has been shown that B. disticha is one of the commonly used plants to “clean the system” but frequently results in the death of the patient. Abrus precatorius contains one of the most toxic compounds known to mankind, namely abrin that collectively refers to a group of glycoproteins. The seeds of A. precatorius also contain two indole alkaloids, abrine and hypaphorine. The two alkaloids were fractionated and characterised by LC-MS and NMR. Due to the fact that the instrumentation of the FCL JHB is not suited to the detection of proteins, an LC-ESI-MS method was developed for the detection of the two alkaloids in plant and viscera matrix as markers for A. precatorius. The presence of these two alkaloids was indicated on the TMD system (EI spectra) in a suspected herbal poisoning case. The LC-ESI-MS method was applied to the analysis of the samples and the absence of abrine and hypaphorine were proven in the samples. Ricinus communis is similar to A. precatorius in that it also contains a group of extremely poisonous glycoproteins, collectively refered to as ricin. The analysis of R. communis seeds encountered the same problems as the analysis of A. precatorius seeds, and the analysis was again focused on the detection of the minor piperidine alkaloid ricinine. The LC-ESI-MS method developed for abrine was modified to detect ricinine and functioned well in botanical and viscera matrices. This method will enable the forensic analyst to detect ricinine in very low levels when the presence of ricinoleic acid in samples indicates the use of a R. communis-based product. Nerium oleander is a common decorative garden plant that is used medicinally. The plant is rich in cardenolides with oleandrin the main compound. A reversed-phase chromatographic method with ESI mass spectral detection was developed to separate and detect 11 cardiac glycosides. The compounds were adequately separated to allow unambiguous identification, and displayed very stable cationisation with sodium. An extraction method was developed to extract the cardiac glycosides from the leaves of N. oleander and Thevetia peruviana and was also evaluated in a viscera matrix. The extraction method functioned well and extracted a variety of compounds that produced unique chromatographic fingerprints, allowing for the easy differentiation between the two plants. The method is ideally suited for the detection of oleandrin in high concentrations (full scan mode), low concentrations (selected masses) or trace levels (SIM analysis of ion clusters). The method is able to distinguish between extracts derived from N. oleander and T. peruviana and was able to detect and confirm neriifolin, odoroside and neritaloside in N. oleander leaf extracts. Analysis of forensic case exhibits were also successfully done with this method and performed well with liquid and solid matrices. With the new method oleandrin could be detected at trace levels in viscera samples that did not produce positive results in the past. Bowiea volubilis is widely used as a medicinal plant, but is also an extremely toxic plant. It is freely available at traditional healer markets, and is one of the most highly traded plants on the Durban market. Despite the high usage of the plant, it has not been detected by any of the forensic laboratories in South Africa. Bovoside A, a bufadienolide, is reported to be the main cardiac glycoside in the bulb of B. volubilis. The cardiac glycoside method was successfully applied to the analysis of the bulb extract of B. volubilis and bovoside A was identified as the main bufadienolide present in the bulb. Bovoside A was fractionated and characterised by LC-MS. Four extracts of botanical origin could be successfully distinguished from each other by monitoring the main masses of bovoside A, oleandrin and thevetin A and thevetin B. These marker compounds were well separated from each other and made the identification of the botanical extracts quite easy, and the identity of each extract was confirmed by the mass spectrum of each peak. / Prof. F.R van Heerden

Background Extensively used grasslands are frequently utilised for hay production for equines. Especially, extensive meadows have a great variety of plant species, which may include plants that are poisonous for equines such as meadow saffron (Colchicum autumnale L.). To authors’ knowledge investigations about horses` avoidance behaviour towards dried meadow saffron in hay are missing. Reports of farmers are contrary to clinical symptoms described in case reports and associated with meadow saffron in hay. Objectives The aim of this study was to determine the rejection behaviour of horses for hay contaminated with meadow saffron (MS) when fed ad libitum. Study design An 18-day feeding trial with six adult geldings to observe the rejection behaviour for hay contaminated with MS. Methods The horses were fed a basal diet containing hay ad libitum and a mineral supplement during the feeding trial. At six different daytimes, hay contaminated with 1% or 2% dried MS was provided to the horses over a duration of 1 h. The rejection behaviour was observed personally and by video recordings. If a horse ingested more than two plants of MS during one observation period, the observation was stopped and repeated at another day. When the observation period had to be stopped twice, the horse was excluded from the experiment. Results Five of six horses ingested MS during the first feeding periods. One horse rejected leaves and capsules at the beginning of the study, but it showed repeated ingestion of MS after the seventh observation period. Main limitations Lack of knowledge about secondary plant metabolites affecting taste and their variability between fresh and dried plants. Conclusions The intake of MS in hay by horses could not be ruled out with certainty. Therefore, feeding hay contaminated with MS should be avoided for equids.

The aim of the thesis titled "Substances contained in Plants of the Nightshade Family (Solanaceae) and their Usage in Biology Teaching" is to familiarize the reader with basic toxicological and pharmacological terms contained in the information on Nightshade plants (Solanaceae). Further it introduces Nightshade plants (Solanaceae) and their substances in more detail. It describes the use and abuse of these plants in poisoning, usage in traditional medicine, homeopathy and modern medicine. It outlines the history of the use and especially abuse of plants containing alkaloids. It also describes options for didactic use through laboratory work and assesses and compares the quality of information available in the literature for high school students. Information contained in this work can be practically used in teaching subjects such as toxicology, pharmacology and pharmacognosy at secondary schools with focus on the chemical and pharmaceutical industry. Key terms: Content Substances, Plant Alkaloids, Poisonous Plants, The Use and Abuse of Solanaceous Plants.

This study was undertaken as a result of the occurrence of a large number of deaths among the local Black population from the use of herbal medicines prepared from the rootstock of Callilepis laureola known to the Zulus as impila. The salient clinico-pathological features in these cases were hypoglycaemia, centrilobular zonal liver necrosis and acute renal tubular necrosis. The purpose of this study was to investigate fully the clinical, biochemical and pathological aspects of the toxicity produced by Callilepis laureola (impila). The first part of the investigation consisted of an assessment of all cases of death due to acute liver necrosis diagnosed by necropsy at King Edward VIII Hospital, Durban. A review of clinical and necropsy records of 21687 consecutive post-mortems performed on Black patients during a 20 year period showed that acute liver necrosis was the major contributing cause of death in 447 patients. In 263 cases the hepatic lesion was centri lobular zonal necrosis with associated acute tubular necrosis (Group A); while in 184 cases the I iver necrosis was of the massive or submassive type (Group B). A comparative assessment of these two groups as regards necropsy prevalence, age and sex distribution and the clinical, biochemical and pathological findings was undertaken. This study shows that the combination of hypoglycaemia, centri lobular zonal liver necrosis and acute renal tubular necrosis due to Callilepis laureola (impila) poisoning is a distinct clinico-pathological entity and differentiates this group from cases of acute massive and submassive liver necrosis resulting in most cases from fulminant viral hepatitis. In the search for the toxic components of the root of Callilepsis laureola several compounds were isolated. These were atractyloside, carboxyatractyloside, two thymol related oils and a carbohydrate. The thymol related oils as well as the carbohydrate were found to be non-toxic in laboratory rats. The crude methanol extract of the root of Callilepsis laureola, when injected intraperitoneally into laboratory rats, produced centrilobular zonal liver necrosis and acute renal tubular necrosis, the lesions identical to those seen in patients who had died after intake of impila prescribed by witchdoctors and other dispensers of herbal medicines. On the other hand intraperitoneal injections of the purified compound atractyloside caused acute renal tubular necrosis and hypoglycaemia in laboratory rats but failed to produce liver necrosis. Carboxyatractyloside also failed to cause liver necrosis. This indicated that there may be at least two toxins contained in the rootstock of Callilepsis laureola, one causing the liver lesion and the other (atractyloside) causing nephrotoxicity and hypoglycaemia. Repeated attempts at isolating the hepatotoxin have failed; the liver toxin or toxins being lost during the process of extraction and purification. Identification of the hepatotoxin awaits further investigation. It is possible that the liver necrosis may be caused by a metabolite or that it may be a synergistic effect of two or more compounds. / Thesis (MD)-University of Natal, 1983.

Made available in DSpace on 2016-12-08T16:24:22Z (GMT). No. of bitstreams: 1 PGCA10MA180.pdf: 4478459 bytes, checksum: 6a32501ee3779e2d35231ab3dac3f5c3 (MD5) Previous issue date: 2010-01-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A disease of cattle with clinical and pathological presentation of acute myopathy was studied in the cities of Bom Jesus and Xanxerê in the State of Santa Catarina. Clinically, the disease was characterized by difficulty in walking, recumbency and death within 2 to 13 days after the onset of clinical symptoms. At necropsy were observed pale areas in the skeletal muscles mainly in the muscles of the hindquarters and the scapular area. The main microscopic lesions were hyaline degeneration and necrosis with fragmentation of the fibers, accompanied by mononuclear cell infiltrates. In the property there was great amount of S. obtusifolia that demonstrated that was consumed by the animals. The disease was reproduced experimentally in cattle fed with green leaves and pods of Senna obtusifolia in daily doses of 8g/kg (4 days), 10 g / kg (5 days), 15 g / kg (3 days) and a single dose 30g / kg body weight. This study aimed to evaluate the epidemiological and clinical lesions of a disease that affects the skeletal muscles of cattle and experimentally reproduce the disease through the administration of leaves and pods of Senna obtusifolia / Uma doença de bovinos com quadro clínico patológico de miopatia aguda foi estudada nos municípios de Xanxerê e Bom Jesus, SC. Clinicamente a enfermidade caracterizou-se por dificuldade em caminhar, decúbito esternal e morte entre dois a 13 dias após o inicio dos sinais clínicos. Um dos bovinos se recuperou e voltou a andar. Na necropsia foram observadas áreas pálidas na musculatura esquelética principalmente nos músculos dos membros posteriores e da região escapular. Ao exame microscópio, a principal lesão foi degeneração hialina e necrose com fragmentação das fibras, acompanhadas de infiltrado mononuclear. Na propriedade havia grande quantidade de S. obtusifolia com sinais de ter sido ingerida A doença foi reproduzida experimentalmente em bovinos com a administração de folhas e vagens verdes de Senna obtusifolia em doses diárias de 8g/kg (4 dias), 10g/kg (5 dias), 15g/kg (3 dias) e em dose única 30g/kg de peso vivo. O objetivo do presente trabalho foi avaliar os aspectos epidemiológicos clínicos e lesionais da enfermidade que afeta a musculatura esquelética dos bovinos e reproduzir experimentalmente a doença através da administração de folhas e vagens de Senna obtusifolia