published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

No description available.

Thesis (Ph.D.) - University of Queensland, 2004. / Includes bibliography.

The isolation and identification of pyrrolizidine alkaloids from various plant species from 1988 to May 1991 are reviewed and the alkaloids of two indigenous plant species, Senecio speciosus Willd and Senecio macrocephalus DC, were investigated. A brief review of the methods used for isolation and identification of pyrrolizidines is also given. S. speciosus was found to contain two new alkaloids, 7-senecioyl-9-sarracinylheliotridine and 7-isosarracinyl-9- sarracinyl-heliotridine, which were identified using highfield NMR techniques. A number of other alkaloids were tentatively identified using GC-MS. S. macrocephalus contains very little alkaloid, but a number of pyrrolizidine alkaloids were tentatively identified using GC-MS. Standard alkaloids for GC-MS work were obtained both by extraction from a number of plant species and by synthesis of simple monoester alkaloids. In this process the alkaloid neosarracine, previously described by GC-MS, was isolated and NMR data for this compound are reported for the first time. S. speciosus and S. macrocephalus are morphologically very similar and their counterparts in the Grahamstown district exhibit features characteristic of both species. This could be due to hybridization, genetic mutation or simple variation within the species. The alkaloids of four local plant populations were examined in order to collect taxonomic markers whereby it was hoped that the Grahamstown plants could be satisfactorily classified. Three of the plant populations were found to contain 7-senecioyl-9-sarracinylheliotridine and 7-angelyl-9-sarracinyl-heliotridine. One population was found to contain the known alkaloid retrorsine along with the new alkaloid 2-hydroxy-l, 2-dihydrosenkirkine. The alkaloidal fractions of all four populations were compared using GC-MS and NMR techniques. Tentative taxonomic conclusions were drawn.

No description available.

Monocrotaline is a pyrrolizidine alkaloid found in plants implicated in livestock and human poisoning. Laboratory rats given monocrotaline develop pulmonary hypertension and right heart hypertrophy in the weeks following administration of the chemical. Lung weight increases and right heart hypertrophy correlate with increased pulmonary artery pressure. Rats which consumed monocrotaline drinking water (20 mg/l) for only 4 days developed significant increases in lung and heart weights 14 days after exposure began. This exposure was equivalent to a dose of 15 mg/kg. Other treatment combinations of time (0-10 days exposure) and monocrotaline concentration (5-60 mg/l in drinking water) were tested. The accumulative dose calculated for each of the treatment combinations which produced toxicity was in the range of 15 to 20 mg/kg. Monocrotaline injury appears to be cumulative, but organ weight increases reverse once exposure is stopped. As pulmonary hypertension develops and pulmonary arteries hypertrophy, the force with which isolated pulmonary artery segments contract decreases. This is a loss of efficacy rather than potency to the contracting agents KCl, norepinephrine, and 5-hydroxytryptamine. Relaxation of arteries under conditions of potassium-return (a measure of Na⁺/K⁺ ATPase activity) was also altered by monocrotaline treatment. In vivo monocrotaline treatment had little effect on the force of K⁺-return relaxation. However, the rate at which arteries relaxed was significantly decreased following 4 days ingestion of monocrotaline drinking water (20 mg/l). In vitro ouabain treatment and endothelial injury also decreased the rate of K⁺-return relaxation. Another Na⁺/K⁺ ATPase activity, ⁸⁶Rb⁺ uptake, was decreased following monocrotaline treatment only when 5-hydroxytryptamine was present and only uptake associated with the endothelium was affected. These studies utilized a very low exposure to monocrotaline (4 days ingestion of 20 mg/l monocrotaline drinking water or 15 mg/kg) to produce toxicity in rats. Monocrotaline-induced toxicity measured 20 days after treatment included right heart and lung hypertrophy and decreased contractions of isolated pulmonary arteries. Monocrotaline treatment decreased the rate of Na⁺/K⁺ ATPase-dependent relaxation of isolated pulmonary arteries 4 days after treatment began.

Ruan, Jianqing. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 162-175). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

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

Graduation date: 1994

Food frequency questionnaire and 24-hour recall methods were used to assess the general consumption of leafy vegetables and fruits within the Luo of northern Tanzania. The frequency questionnaire focused specifically on the consumption of Crotalaria brevidens, a leafy vegetable in a genus characterised by toxic pyrrolizidine alkaloids. Leafy vegetables were the most frequently consumed food group, contributing 23% of the total frequency scores. Crotalaria brevidens contributed 1.7% of the total frequency scores although some individuals consume significantly more. High consumption frequency of Crotalaria sp. is negatively associated with the consumption of fruits, fats and oils, vitamin A animal sources and consumption of animal products. Edible portions of Crotalaria sp. contain toxic pyrrolizidine alkaloids detected by thin layer chromatography. HPLC analysis showed that the plant contains high amounts of $ beta$-carotene. Quantification of the toxic alkaloids was not possible due to the low sensitivity of the methods used and low quantities present in the edible portions. Based on reported detection limits for the methods used a low and high estimated intake of toxic alkaloids was calculated and risk/benefit is assessed in relation to its nutrient content.