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Species difference in bioactivation and detoxification of pyrrolizidine (senecionine) alkaloidsHuan, Jianya 31 March 1995 (has links)
Graduation date: 1995
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Macrocyclic pyrrolizidine alkaloids the total synthesis of (±)-crispatine and (±)-fulvine /Larsen, Scott Douglas. January 1984 (has links)
Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.
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Metabolism of pyrrolizidine alkaloids by ruminal microbesHovermale, Jeannette Talbot 22 January 1998 (has links)
Graduation date: 1998
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Immunotoxicity of the pyrrolizidine alkaloid monocrotaline in C57B1/6 miceDeyo, James A. 29 October 1991 (has links)
Monocrotaline (MCT) is a member of a class of naturally occurring
phytotoxins known as pyrrolizidine alkaloids (PAs). Exposure to PAs can result
in liver and cardiopulmonary lesions as well as lymphoid organ atrophy. In the
present study C57BI/6 (B6) mice received MCT (0-150 mg/kg/day, po) for 14
days. Overt toxicity was minimal and observed only at highly immunosuppressive
doses. Following MCT exposure, significant dose-dependent suppressions
were observed in the following immune responses: numbers of antibody
producing cells, cytotoxic T- lymphocyte activity, and NK cell cytotoxicity. The
antibody responses to the T cell-dependent antigen, SRBC, and the T cell-independent
(TI) antigens, DNP-Ficoll and TNP-LPS, were decreased with
identical dose response curves. This, along with data showing MCT decreased
blastogenesis of B cells more than T cells at the lowest dose level, and that high
doses induced significant decreases in the total number of B cells only, suggest
that the B cell may be more sensitive than T cells, NK cells , or macrophages.
The liver and lung toxicity of MCT is believed to be mediated through its
metabolism by mixed function oxidase (MFO) enzymes to reactive pyrroles
(monocrotaline pyrrole, MCTP; and dihydropyrrolizine, DHP). Accordingly, it
was our hypothesis that the immunotoxicity could be modulated by altering MFO
activity. To test this, mice were given a single dose of MCT (100 or 200 mg/kg,
po) after MFO induction with phenobarbital; in other experiments mice received
the MFO inhibitor chloramphenicol immediately before and 3 hrs after a single
exposure to MCT (300 mg/kg, po). However, neither MFO induction nor
inhibition significantly altered the immunosuppressive potency of MCT. The
antibody and blastogenic responses of splenic lymphocytes directly exposed to
MCT (1-3 mM) or MCTP (1-8 μM) in culture were inhibited in a concentration-dependent
manner, indicating that both parent and metabolite were immunotoxic.
However, the inability to alter the in vivo immunotoxicity by altering MFO
activity questions the role this metabolite may play in vivo. In conclusion, the
immune system in B6 mice is a sensitive target of MCT toxicity. Inhibition of
blastogenesis appears to be one mechanism of MCT-induced immunosuppression.
In contrast to other toxic effects of MCT, our results suggest that the parent
compound itself plays a significant role in the immunotoxicity. / Graduation date: 1992
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Metabolism of pyrrolizidine alkaloids by ruminal microbesHovermale, Jeannette Talbot 22 January 1998 (has links)
The plant Senecio jacobaea (tansy ragwort) produces several macrocyclic
pyrrolizidine alkaloids which cause irreversible liver cirrhosis. All of the pyrrolizidine
alkaloids in Senecio jacobaea are macrocyclic diesters of the necine base
retronecine, with the two most predominant being seneciphylline and jacobine.
Unlike horses and cattle, sheep and goats are generally resistant to chronic
pyrrolizidine alkaloid toxicosis due to metabolism of the toxic pyrrolizidine alkaloids
by ruminal bacteria.
In this study, metabolism of jacobine and seneciphylline by ruminal bacteria
was investigated, focusing on two possible metabolic pathways. One pathway
involved hydrolysis of jacobine and seneciphylline and the subsequent production
of the necine base retronecine. For use in these studies, retronecine was isolated
and labeled with deuterium. A method was developed for the determination of
retronecine to 0.02 μg /mL. Significant hydrolysis of jacobine and seneciphylline
was not observed in either ovine whole rumen fluid or with a mixed culture of
anaerobic microbes derived from ovine rumen fluid which metabolizes jacobine and
seneciphylline. Direct metabolism of retronecine independent of the macrocyclic
pyrrolizidine alkaloids was also not observed.
The second metabolic pathway studied involved the production of the necine
base modified by the conversion of the 1,2-double bond to an external methylene
group. Previously this conversion has been observed during metabolism of
pyrrolizidine alkaloids by the organism Peptostreptococcus heliotrinreducens. In
this study, P. heliotrinreducens was used to convert the pyrrolizidine alkaloids
heliotrine and lasiocarpine to the known 1-methylene-pyrrolizidines. The mixed
culture of ovine anaerobic microbes also metabolized heliotrine and lasiocarpine
rapidly to identical methylene products. This mixed culture metabolized jacobine
and seneciphylline rapidly with production of very low levels of the corresponding
1-methylene compounds. In contrast, metabolism of jacobine or seneciphylline by
P. heliotrinreducens was not observed. The mixed culture has demonstrated the
ability to metabolize a greater variety of pyrrolizidine alkaloids than P.
heliotrinreducens.
Although the metabolites of jacobine and seneciphylline were not
conclusively identified, it was determined that hydrolysis of jacobine and
seneciphylline is not occurring. The second pathway studied appears to be more
probable, with the production of 1-methylene compounds as intermediates, although
not as end-products. / Graduation date: 1998
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The determination of the partition coefficients for a variety of pyrrolizidine alkaloids and the relationship of these values to the anti-tumor activity of the alkaloidsRyan, Edward Thomas 08 1900 (has links)
No description available.
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Slaframine, australines and castanosperminesSibley, A. William January 1997 (has links)
No description available.
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Synthetic studies on necic acids of pyrrolizidine alkaloidsLee, Nadine Chauyi 06 January 1998 (has links)
Graduation date: 1998
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Effects of dietary pyrrolizidine alkaloids on copper and vitamin A metabolism in the chicken and Japanese quailHuan, Jianya 28 March 1991 (has links)
Objectives of this study were to examine effects of dietary pyrrolizidine alkaloids
(PA) on copper and vitamin A metabolism in the chicken which are very susceptible to
the hepatoxic effects of PA and Japanese quail which are highly resistant to PA. Also,
the possible interaction between copper and vitamin A in the two species and effect of
PA on retention of previously stored vitamin A in the chicken were investigated. Three
experiments were designed. Experiment 1 was to examine the effect of feeding the PA-containing
plant tansy ragwort (TR)(Senecio jacobaea) on tissue levels of copper and
vitamin A in the chicken. Experiment 2 was to investigate if dietary PA affected the
retention of previously stored vitamin A in the chicken. Experiment 3 was to determine
if hepatoxic effects of PA are necessary to influence copper and vitamin A metabolism
in Japanese quail.
In experiment 1, a 2x2x2 factorial design with dietary 0 and 5% TR, 0 and 250 ppm
copper, and 0 and 25,000 IU/kg diet vitamin A was used. The results showed that body
weight gain was reduced (P < 0.01) in birds fed TR. Both serum and liver copper
concentrations were markedly increased (P <0.01) in the TR-fed group with 250 ppm
copper supplement. Zinc concentrations in the serum and liver were significantly
decreased (P <0.05) in the TR-fed groups compared to TR-free groups. Liver iron was
increased (P <0.05) in the TR-fed birds. The serum vitamin A levels were significantly
decreased (P < 0.01) in all TR-fed groups. The ranges of decrease were from 62 to 72
% in four TR -fed groups. The liver vitamin A concentrations were also significantly
decreased (P <0.05) in TR-fed groups without vitamin A supplement. The effects of PA
on liver and blood vitamin A concentration may reflect PA inhibition of synthesis of
retinol-binding proteins, or impaired vitamin A absorption from reduced biliary
excretion. There was no interaction between dietary copper and vitamin A levels and
tissue concentrations of these nutrients.
In experiment 2, a two period experiment was carried out. In the first period, two
groups of chicks were fed a diet containing 25,000 IU vitamin A/kg diet for two weeks
followed by a control or TR-containing diet for four weeks. Blood samples were taken
at 4 day intervals for 24 days. It was found that by day 8, serum vitamin A levels were
significantly depressed (P <0.05). After 24 days of PA exposure, serum vitamin A levels
were reduced by 55 % and 8.5% in the TR-fed group and the control group, respectively.
Liver concentration of vitamin A was increased (P < 0.05) at day 24 of TR feeding, while
liver vitamin A concentration in birds fed the control diet was decreased by 13% over
the same period. The results indicate that PA inhibit the mobilization of previously stored
vitamin A from the liver, probably by inhibiting hepatic synthesis of retinol-binding
proteins.
Experiment 3 was a 2x2x2 factorial design with added 0 and 5% tansy ragwort, 0
and 250 ppm copper, and 0 and 25,000 IU/kg diet vitamin A. The results showed that
consumption of TR did not affect the growth rate of Japanese quail. There were no
significant differences in the serum copper concentrations among all treatment groups.
Liver copper levels were decreased with TR feeding (P <0.05). The concentrations of
zinc and iron in the serum and liver were normal in TR-fed groups compared to the
controls. There was no significant effect (P >0.05) on the serum vitamin A
concentration. The liver vitamin A concentrations were also not significantly different
with the exception of the basal TR group. Copper supplementation of the diet increased
serum vitamin A levels (P <0.05). The results suggest that hepatotoxicity is necessary
to induce the changes in tissue levels of copper and vitamin A seen in PA-susceptible
species. / Graduation date: 1991
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I. SYNTHETIC APPLICATIONS OF CARBANIONS DERIVED FROM GLYCOLATES--STUDIES DIRECTED TOWARD THE SYNTHESIS OF VITAMIN-C; II. CRYSTAL AND MOLECULAR STRUCTURE OF SYN-9-HYDROXY-1-AZA-4-OXATRICYCLO (3.2.1.1(3,8)) - NONANE--A BRIDGED PYRROLIZIDINEDeardorff, Donald Ross January 1979 (has links)
No description available.
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