Thesis (Ph. D.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains ix, 134 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.

Thesis (M.S.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains viii, 62 p. : ill. (some col.) Vita. Includes abstract. Includes bibliographical reference.

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

Thesis (M.S.)--West Virginia University, 2006. / Title from document title page. Document formatted into pages; contains viii, 59 p. : ill. Vita. Includes abstract. Includes bibliographical references.

Thesis (Ph. D.)--Oregon State University, 2007. / Printout. Includes bibliographical references (leaves 52-64). Also available on the World Wide Web.

Endophyte-infected tall fescue produces many ergot alkaloids, which have been shown to be vasoconstrictive in various vessel types of bovine. On the other hand, substantial evidence has been reported on the vasodilative effects of formononetin and biochanin A in different vessel types in humans and rats. So, a study was conducted using mesenteric vasculature collected from heifers shortly after slaughter. After 2-h incubation with formononetin (F), biochanin A (B), or an ergovaline-containing tall fescue seed extract (EXT) and their combinations, vessels were mounted in a multi-myograph to determine their ergotamine-induced contractility. Results indicated that F and B at 1 × 10-6 M and their combination did not impact the contractile response to ergotamine in mesenteric vasculature. The pre-myograph incubation of mesenteric vasculature with EXT altered the contractile response manner to ergotamine. However, at higher concentration, F and B may alleviate the reduction of vasoconstriction caused by prior exposure to EXT. To our knowledge, this study was the first to investigate the interaction of ergot alkaloids and isoflavones on in vitro bovine mesenteric vasculature. However, further investigations are necessary to understand the mechanism behind the interaction of ergot alkaloids and isoflavones on vasoactivity.

Thesis (M.S.)--Oregon State University, 2008. / Printout. Includes bibliographical references (leaves 73-86). Also available on the World Wide Web.

The present investigation was designed to investigate the use of blessed thistle (Cnicus benedictus) in amelioration of fescue toxicosis in beef cattle. Twenty-seven crossbred Angus cows were blocked by age and weight into groups of three. Each group (n=9) was then randomly assigned to one of three dietary treatments: endophyte-free (EF), endophyte-infected (EI), or endophyte-infected with addition of cut and stemmed blessed thistle (EIBT). Each group was also randomly assigned to one of three 29-day replicates. Parameters measured during this trial included: urinary ergot alkaloid concentration (ng ergot alkaloids/mg creatinine), body weight (kg), rectal temperature (°C), serum progesterone (ng/ml), and serum prolactin (ng/ml). No effect of treatment (P>0.05) was detected in any of these parameters. A treatment x time interaction (P<0.0001) was observed for progesterone concentrations, likely a result of estrous cyclicity of cows. Results of this study suggest that we were unsuccessful in inducing fescue toxicity in test subjects assigned to EI and EIBT treatments. Minimal dietary ergovaline (1.72 μg kg-1) and cool ambient temperatures (-6.7°C to 23.3°C) likely contributed to this inability. Data from this research do suggest, however, that C. benedictus can be successfully incorporated into cattle diets. Further research will need to be performed to fully elucidate what, if any, benefits blessed thistle can have in the treatment of fescue toxicity.

Fescue toxicosis is problematic for ruminant livestock, causing weight loss and low productivity when fed endophyte-infected forages. Complete underlying mechanisms of toxicosis are unknown therefore; the objective of the study was to determine if ruminally dosed ergot alkaloids impact rumen motility. Cannulated steers were pair-fed a forage diet and ruminally dosed with endophyte-free (E-) or endophyte-infected (E+) tall fescue seed. An 8-h period of rumen motility collection began 4-h after feeding by monitoring pressure change via a wireless telemetry and transducer system. In experiment 1, steers were paired by weight and assigned to E- or E+ treatment. Overall, E+ steers had more frequent contractions. On d 7 - 9, both treatments had lower frequencies and E- steers had greater amplitude of contractions, which corresponded with decreased DM intake. In experiment 2 steers remained in pair, but switched treatment. During the 57 d E+ steers received titrated levels of ergovaline + ergovalinine. There was no difference between treatments for frequency or amplitude of contractions, but increasing dosage, decreased frequency (d 1 - 44) and amplitude, coinciding with lower DM intakes. Alteration in rumen motility associated with changes in intake may be responsible for the decreased productivity in ruminants consuming E+ forages.

Tall fescue is a widely grown, cool season grass prevalent in the eastern United States that is known for its resistance to abiotic and biotic stresses. A main reason for tall fescue's resistance to these stresses is attributed to the presence of a fungal endophyte. Unfortunately, this endophyte also adversely affects cattle production. Cows consuming the ergot alkaloids produced by these endophytes can exhibit decreased feed intake, growth performance, organ vasoconstriction, and increased rectal temperature. This work is interested in examining how endophyte toxin exposure impacts pregnancy in cattle. Reduced blood flow to the fetus and inadequate maternal nutrition contributes to intra uterine growth restriction (IUGR), and this work proposed that fescue endophyte toxicity affects the gestating cow and fetus. Three studies were completed. In experiment 1, gestating cows grazed high or low endophyte fescue pastures during late gestation to determine if exposure to ergot alkaloids in utero results in IUGR and if calves from these pregnancies have altered growth performance. Creep feeding was evaluated as a mitigation strategy for impaired calf growth due to fescue toxicity, and feedlot performance was evaluated to determine if consuming fescue during gestation and creep feeding would affect feedlot performance. Calf BW was different (P < 0.01) by treatment x time. Birth weights of calves were similar , prior to creep feeding calves exposed to high endophyte fescue were lower, and post-supplementation creep fed calves had increased BW. Days on feed and dressing percentage were decreased in the supplemented group, and marbling score was decreased for both the supplemented and unsupplemented groups following the completion of the feedlot phase (P < 0.05). The second study was setup similar to study one, however cows were exposed to fescue pastures from d 170 of gestation until calving. Calf birth weights did not differ, but weights were increased in the supplemented group post creep feeding (P < 0.05). Average daily gains (ADG) of supplemented calves were greater during the supplementation period (P < 0.01). In the third study, indwelling vaginal temperature probes were used to evaluate differences in body temperature of cows fed fescue seed with high or low levels of ergot alkaloids during early gestation, and in varying environmental conditions. In the winter trial, body temperature was measured hourly from days 0-14 of gestation. In the summer trial, body temperature was measured hourly from days 0-32 of gestation. Body temperatures were different (P < 0.01) between treatments during both trials. / Master of Science