1 |
GENOTOXICITY OF THE PYRROLIZIDINE ALKALOIDS: ASSOCIATION WITH ADVERSE HEPATIC EFFECTS (ALKALINE ELUTION, CHEMICAL CARCINOGENESIS, ANTIMITOTIC EFFECTS).PETRY, THOMAS WILLIAM. January 1984 (has links)
Pyrrolizidine alkaloids (PAs) produce a variety adverse hepatic effects, including acute toxicity, carcinogenicity and potent, persistent antimitotic effects. Additionally several have been evaluated as antineoplastic agents. PAs constitute significant health hazards to man and domestic animals. The mechanism(s) by which PAs induce these effects are not known. These studies were designed to test the hypothesis that some or all of the adverse hepatic effects and possibly the antineoplastic activity of PAs associate with or are mediated by a genotoxic interaction with cellular DNA. The first objective of the studies was to verify the in vivo gentoxicity of the PAs, in the process characterizing the type(s) of DNA damage induced. Hepatic DNA damage induced by the model PA monocrotaline (MCT) was assessed following i.p. administration to adult male Sprague-Dawley rats. DNA damage was characterized by the alkaline elution technique. MCT was found to induce both DNA-DNA interstrand and DNA-protein cross-links. No evidence was seen for the induction of DNA single-strand breaks, although the presence of small numbers of DNA single-strand breaks could have been masked by the overwhelming predominance of DNA cross-links. DNA-DNA interstrand cross-linking reached a maximum within 12 hr and thereafter decreased over a protracted period. By 96 hr post administration, the calculated cross-linking factor was no longer statistically different from zero (control). Further studies were performed to test the effects of agents known to modulate the formation/disposition of the proposed reactive intermediate and the toxic effects of the PAs. Consistent with its involvement in the mechanism of the toxicity of the PAs, genotoxicity was shown to modulate in the same direction and to similar degree as does the toxicity. Other PAs, or derivatives thereof, were evaluated in addition to MCT. Structural requirements for DNA cross-linking potential were shown to be similar to those required for the induction of toxic and antimitotic effects, again consistent with the involvement of DNA cross-linking in the mechanism of these effects. Indicine N-oxide however, an experimental antineoplastic agent, was shown not to mediate its cytotoxic effects via this mechanism.
|
2 |
Bacterial 16S ribosomal DNA analysis of pyrrolizidine alkaloid detoxifying enrichments from the ovine rumenGray, Diane R. 05 February 1998 (has links)
Bacterial cultures enriched from sheep rumen fluid have demonstrated the ability
to detoxify pyrrolizidine alkaloids (seneciphylline and jacobine) in tansy ragwort
(Senecio jacobaea). The microbes are difficult to isolate using classical anaerobic
techniques, therefore, microbes from two different enrichment cultures demonstrating
similar degradation activity were identified using their 16S ribosomal RNA genes. Gene
sequences from a rich medium enrichment were matched to Clostridium bifermentans,
Prevotella ruminicola, Escherichia coif, and from a minimal medium enrichment to, C.
clostridiiforme, C. aminophilum, Streptococcus bovis, and Butyrivibrio fibrosolvens.
There were no identical organisms between the two libraries, but the common genus was
Clostridium. / Graduation date: 1998
|
3 |
THEOPHYLLINE SERUM CONCENTRATIONS IN AMBULATORY PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE.Bredon, James Wolfe. January 1982 (has links)
No description available.
|
4 |
Metabolism of toxic plant alkaloids in livestock : comparative studies on the hepatic metabolism of pyrrolizidine alkaloids in sheep and cattle and of ergot alkaloids in an endophyte-resistant mouse modelDuringer, Jennifer Marie 30 April 2003 (has links)
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
|
5 |
Evaluation of endophyte-infected tall fescue products, their interaction with Senecio jacobaea in ruminants, and detoxification of alkaloids by ammoniation or ensiling after grindingDebessai, Woldu T. 26 August 1997 (has links)
Graduation date: 1998
|
Page generated in 0.0661 seconds