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
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/31167 |
| Date | 30 April 2003 |
| Creators | Duringer, Jennifer Marie |
| Contributors | Craig, A. Morrie |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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