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
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/37219 |
| Date | 22 January 1998 |
| Creators | Hovermale, Jeannette Talbot |
| Contributors | Craig, A. Morrie |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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