The effect of 7,8-methylenedioxylycoctonine-type diterpenoid alkaloids on the toxicity of methyllycaconitine in mice

Larkspur plants contain numerous norditerpenoid alkaloids, which include the 7,8-methylenedioxylycoctonine (MDL)-type alkaloids and the N-(methylsuccinimido)anthranoyllycoctonine (MSAL)-type alkaloids. The MSAL-type alkaloids are generally much more toxic (typically >20 times). Toxicity of many tall larkspurs, such as Delphinium barbeyi, has been attributed to its large concentration of MSAL-type alkaloids, including methyllycaconitine (MLA). However, the norditerpenoid alkaloids found in the greatest concentrations in most D. barbeyi populations are either deltaline or 14-O-acetyldictyocarpine (14-OAD), both less toxic MDL-type alkaloids. Although the individual toxicities of MLA, 14-OAD, and deltaline have been determined, the impact (additive or antagonistic) that large concentrations of deltaline or 14-OAD in the plant have on the toxicity of MLA is unknown. Consequently, the effect of MDL-type alkaloids on the toxicity of MLA was compared by using median lethal dose (LD(50)) and toxicokinetic profiles of the brainand muscle from mice receiving i.v. administration of these alkaloids, individually or in combination, at ratios of 1:1, 1:5, and 1:25 MLA to MDL-type alkaloids. The LD(50) for MLA alone was 4.4 +/- 0.7 mg/kg of BW, whereas the coadministration of MLA and deltaline at 1:1, 1:5, and 1:25 resulted in an LD(50) of 2.7, 2.5, and 1.9 mg/kg of BW, respectively. Similarly, the coadministration of MLA and 14-OAD at 1:1, 1:5, and 1:25 resulted in an LD(50) of 3.1, 2.2, and 1.5 mg/kg of BW, respectively. Coadministration of mixtures did not result in increased MLA bioavailability or alterations in clearance from the brain and muscle. Consequently, the increased toxicity of the mixtures was not a result of increased MLA bioavailability (based on the maximum concentrations observed) or alterations in MLA clearance from the brain and muscle, because these were unchanged. These results demonstrate that MDL-type alkaloids have an additive effect on MLA toxicity in mice and may also play a role in the overall toxicity of tall larkspur plants in cattle.     

Description of a scale for rating the clinical response of cattle poisoned by larkspur

Larkspur poisoning is a major cause of acute death of cattle on mountain and high plains rangelands of western United States. A nonlethal method to quantify dose response in cattle is needed to better estimate the toxicity of larkspur plants and the response of cattle to larkspur poisoning and to provide a basis for reference during studies. A numerical system of rating the clinical signs of larkspur poisoning was developed and used to describe the response of 10 Hereford cows given a repeated single daily dose of larkspur (Delphinium occidentale x barbeyi) by gavage. Larkspur poisoning resulted from a short-term cumulative effect, and a statistically significant increase in score was essentially maximal by 4 days. At the dose given, this effect did not persist for more than 4 days after cessation of dosing. Poisoning was most severe between 5 and 9 hours after dosing. Early signs of poisoning can be subtle and sometimes brief. The effect of larkspur poisoning can be exacerbated temporarily by exertion. Therefore, cattle could probably repeatedly consume an otherwise toxic daily dose, without manifesting marked signs of poisoning, if consumption decreased to a sufficient degree intermittently at 2- to 4-day intervals.     

Plant-animal interactions in larkspur poisoning in cattle

Larkspur (Delphinium spp.) toxicity in cattle seriously impedes the efficient use of productive mountain rangelands. Larkspurs contain complex diterpenoid alkaloids that cause acute intoxication and death from respiratory paralysis. Alkaloids and their concentrations vary among larkspur species, plant parts and phenological growth stages, thus causing great variability in toxicity. Ingestion rate of larkspur by the cow, alkaloid toxicity and concentration in the plant and the kinetics of absorption and excretion interact to determine whether a cow is poisoned. Plant and animal factors influencing consumption and subsequent intoxication must be further elucidated to devise management strategies to reduce liverstock losses.     

Toxic Alkaloid Concentrations in Delphinium Nuttallianum,Delphinium Andersonii,and Delphinium Geyeri in the Intermountain Region

Low larkspurs (Delphinium nuttalliunum Pritz., Delphinium andersonii Gray) and plains larkspur (Delphinium geyeri Greene) often poison cattle grazing on western North American rangelands. The dominant toxic alkaloid in larkspur is methyllycaconitine (MLA); other very toxic alkaloids in low and plains larkspurs are nudicauline and geyerline. Toxic alkaloid concentrations in larkspur near or above 3 mg · g^-1 present significant risk to grazing cattle. D. nuttallianum from Utah and Colorado, D. andersonii from northern Arizona, and plains larkspur (D. geyeri) from Wyoming were collected for analysis. Concentrations of MLA in D. nuttallianum ranged from 0.8 to 4.5 mg · g^-1 in Utah and Colorado; total toxic alkaloid concentrations were often above 3 mg · g^-1. D. nuttallianum differed (P = 0.09) in MLA concentration between locations but not phenological stages (P = 0.41). Concentrations of nudicauline ranged from 0.7 to 4 mg · g^-1 in D. nuttallianum and were different (P = 0.01) between locations and phenological stages (P = 0.004). D. andersonii was consistently toxic because the total toxic alkaloid concentration fluctuated from 3 to 6 mg · g^-1 over the growing season. The concentration of geyerline in D. andersonii was equal to or greater than MLA at each phenological stage, thus adding to the toxicity. The concentration of toxic alkaloids in D. geyeri was typically highest (2–4 mg · g^-1) in immature plants, although toxic alkaloid concentrations in plants during the pod stage of growth sometimes increased. Only trace amounts of nudicauline were found in D. geyeri, as most of the alkaloid fraction was other N-(methylsuccinimido) anthranoyllycoctonine (MSAL) alkaloids. Total alkaloid concentration (MSAL and non-MSAL alkaloids) in D. geyeri sometimes exceeded 15 mg · g^-1. Concentrations of toxic alkaloids in D. nuttalliunum, D. andersonii, and D. geyeri often did not significantly decline during the growing season as typically found in tall larkspurs. Thus, risk to grazing cattle may remain high until these plants are dormant.     

Toxicokinetics of norditerpenoid alkaloids from low larkspur (Delphinium andersonii) orally administered to cattle

Objective-To determine the toxicokinetics of N-(methylsuccinimido)anthranoyllycoctonine-type low larkspur alkaloids in beef cattle. Animals-5 Black Angus steers and 35 Swiss Webster mice. Procedures-Low larkspur (Delphinium andersonii) was collected, dried, ground, and administered to 5 steers via oral gavage to provide a dose of 12 mg of N-(methylsuccinimido)-anthranoyllycoctonine alkaloids/kg. Steers were housed in metabolism crates for 96 hours following larkspur administration; heart rate was monitored continuously, and blood samples were collected periodically for analysis of serum concentrations of 16-deacetylgeyerline, methyllycaconitine, geyerline, and nudicauline and assessment of kinetic parameters. The LD(50) of a total alkaloid extract from D andersonii was determined in Swiss Webster mice. Results-The alkaloids were quickly absorbed, with a maximum serum concentration achieved within 18 hours after administration. Geyerline and nudicauline coeluted as 1 peak and were considered together for toxicokinetic analysis. Mean ± SD elimination half-life was 18.4 ± 4.4 hours, 15.6 ± 1.5 hours, and 16.5 ± 5.1 hours for 16-deacetylgeyerline, methyllycaconitine, and geyerline and nudicauline, respectively. There were significant differences in maximum serum concentration, amount absorbed, and distribution half-life among the 4 alkaloids. The mouse LD(50) was 9.8 mg/kg. Conclusions and Clinical Relevance-Results suggested that clinical poisoning was likely to be most severe approximately 18 hours after exposure. Cattle should be closely monitored for at least 36 hours after initial exposure. Additionally, a withdrawal time of approximately 7 days would be required to clear > 99% of the toxic alkaloids from the serum of cattle that have ingested low larkspur.     

Cattle Grazing Toxic Delphinium andersonii in South-Central Idaho

Anderson larkspur (Delphinium andersonii A. Gray) is a toxic plant responsible for cattle death losses in the western United States. The objectives of the present study were to determine when cattle consumed Anderson larkspur in relation to plant phenology and toxicity, and to determine if animal age influenced selection of Anderson larkspur. These grazing studies were conducted on semiarid sagebrush rangeland near Picabo, Idaho. Eight 6–7-yr-old mature Angus cows were used in 2008, whereas during 2009, 12 Angus cattle were used, including six yearling heifers and six 4-yr-old cows. The overall density of Anderson larkspur was 2.8 plants · m^?2 during 2008, and 4.9 plants · m^?2 during 2009. Total toxic alkaloid concentrations in Anderson larkspur plants were near or above 5 mg · g^?1 during both studies. During 2008 consumption peaked during the late flower and pod stage of growth. Overall in 2008 cows ate 3% of their bites as larkspur. During 2009 heifers ate about twice as much Anderson larkspur as did mature cows (5.1% of bites vs. 2.9%, respectively). Heifers repeatedly consumed sufficient larkspur that they collapsed; however, no animals were fatally intoxicated. Heifers appeared to become transiently averted to larkspur; however, heifers resumed consumption of D. andersonii after a period of one to several days of low or no consumption. Livestock management to reduce losses to Anderson larkspur should include timed grazing to avoid infested pastures during full flower to pod phenological stages, and grazing with older animals rather than yearling heifers.     

Comparison of larkspur alkaloid extract and lithium chloride in maintaining cattle aversion to larkspur in the field.

Lithium chloride (LiCl) and larkspur (Delphinium barbeyi) alkaloid extract were compared in their effect as an emetic to create taste aversions to fresh larkspur. They were further compared in the field to determine whether the indigenous larkspur alkaloids were more effective in maintaining the aversion when conditioned cattle were subjected to the social pressure (social facilitation) of control cattle eating larkspur. Taste aversions were produced in two groups of 1-yr-old cattle by offering fresh larkspur and then gavaging with either LiCl at 200 mg/kg of BW or larkspur alkaloid extract at 1.1 to 1.6 mL/kg of BW. The third group (control) was gavaged with water. The alkaloid group was slower to form an aversion than the lithium group, requiring four doses compared with two doses. All groups were then taken to larkspur-infested rangeland to test the aversion in the field. In the first field trial in which groups grazed separately, both aversion-induced groups generally abstained from eating larkspur. In the second trial in which all groups grazed together, both aversion-induced groups consumed less than half as much larkspur as the controls, but neither group abstained completely. Larkspur alkaloids did not maintain the aversion to larkspur to a greater degree than did LiCl when aversion-induced cattle were subjected to social facilitation.     

The acute toxicity of the death camas (Zigadenus species) alkaloid zygacine in mice, including the effect of methyllycaconitine coadministration on zygacine toxicity

Death camas (Zigadenus spp.) is a common poisonous plant on foothill rangelands in western North America. The steroidal alkaloid zygacine is believed to be the primary toxic component in death camas. Poisonings on rangelands generally occur in the spring when death camas is abundant, whereas other more desirable forage species are limited in availability. In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in that area. One common poisonous plant that is often found growing simultaneously in the same area as death camas is low larkspur (Delphinium nuttallianum). Consequently, the objectives of this study were to conduct acute toxicity studies in mice and to determine if coadministration of low larkspur will exacerbate the toxicity of death camas. We first characterized the acute toxicity of zygacine in mice. The LD(50) of zygacine administered intravenously (i.v.) and orally was 2.0 ± 0.2 and 132 ± 21 mg/kg, respectively. The rate of elimination of zygacine from whole blood was determined to be 0.06 ± 0.01/min, which corresponds to an elimination half-life of 13.0 ± 2.7 min. The i.v. LD(50) of total alkaloid extracts from a Utah and a Nevada collection were 2.8 ± 0.8 and 2.2 ± 0.3 mg/kg, respectively. The i.v. LD(50) of methyllycaconitine (MLA), a major toxic alkaloid in low larkspur, was 4.6 ± 0.5 mg/kg, whereas the i.v. LD(50) of a 1:1 mixture of MLA and zygacine was 2.9 ± 0.7 mg/kg. The clinical signs in mice treated with this mixture were very similar to those of mice treated with zygacine alone, including the time of onset and death. These results suggest that there is an additive effect of coadministering these 2 alkaloids i.v. in mice. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for ranchers and in designing additional experiments to study the toxicity of death camas to livestock.     

Consumption of Low Larkspur (Delphinium nuttallianum) by Grazing Sheep

Low larkspur (Delphinium nuttallianum Pritz.) poisoning causes serious economic loss to livestock producers that graze cattle on foothill and mountain ranges in western North America. In general, all Delphinium spp. are five times less toxic to sheep than to cattle. Because low larkspurs are less toxic to sheep than cattle, grazing sheep before cattle on rangelands with dense populations of low larkspur can reduce larkspur density and risk of poisoning to grazing cattle. All previous published work on sheep and larkspur interactions has involved tall larkspurs. This series of studies was conducted to determine if sheep would consume sufficient low larkspur to reduce subsequent risk to cattle. Four summer trials were conducted in Collbran, Colorado, and Soda Springs, Idaho on pastures with dense (> 9 plants · m^?2) low larkspur populations. In all trials, sheep ate very little low larkspur (< 0.5% of bites). During one final trial using high sheep density (two sheep · 0.015 ha^?1 for 9 d), sheep consumed little low larkspur, but animals appeared to trample much of the low larkspur. Toxic alkaloid concentrations in low larkspur ranged from 1.1 mg · g^?1 to 1.6 mg · g^?1 in all trials. The use of sheep to graze low larkspurs to reduce subsequent consumption by grazing cattle does not appear to be a viable option.     

Effect of Aboveground Mass Removal on Toxicity of Geyer’s Larkspur,with Important Implications for Grazing Management

The many species of larkspur (Delphinium spp. L.) are among the most dangerous poisonous plants on rangelands in the western United States, causing death losses estimated at 2 − 5% (up to 15%) per year for cattle grazing in larkspur habitat. Other effects, such as altered grazing management practices and consequent lost forage quantity and quality, are significant but poorly understood. Current best management practice recommendations are based on seasonal avoidance, with little evidence that this is practical or effective. Our ongoing research has presented evidence that instead it may be possible to manage grazing such that all cattle eat some larkspur, but none eat a fatal dose. This raises the question of the potential response of larkspur to being grazed. In this study we examine the response of Geyer’s larkspur (D. geyeri Greene) to two seasons of 25% or 75% aboveground plant mass removal. The 75% treatment led to significantly lower alkaloid concentrations (mg • g^− 1) and pools (mg per plant), while the 25% treatment had a lesser effect. Combined with lessons from previous studies, this indicates that Geyer’s larkspur plants subject to aboveground mass removal such as may occur via grazing can be expected to become significantly less dangerous to cattle. We suggest that the mechanisms for this reduction are both alkaloid removal and reduced belowground root mass, as significant evidence indicates that alkaloids are synthesized and stored in the roots. These results continue to build support for our theory that the solution to the seemingly intractable challenge of larkspur poisoning lies not in avoidance but in the skill of managers and the wisdom of herds.     

Predatory Plants and Patchy Cows: Modeling Cattle Interactions with Toxic Larkspur Amid Variable Heterogeneity

The most common explanations for the evolution and persistence of herd behavior in large herbivores relate to decreased risk of predation. However, poisonous plants such as larkspur (Delphinium spp.) can present a threat comparable to predation. In the western United States, larkspur diminishes the economic and ecological sustainability of cattle production by killing valuable animals and restricting management options. Recommendations for mitigating losses have long focused on seasonal avoidance of pastures with larkspur, despite little evidence that this is practical or effective. Our ongoing research points to the cattle herd itself as the potential solution to this seemingly intractable challenge and suggests that larkspur and forage patchiness may drive deaths. In this paper, we present an agent-based model that incorporates neutral landscape models to assess the interaction between plant patchiness and herd behavior within the context of poisonous plants as predator and cattle as prey. The simulation results indicate that larkspur patchiness is a potential driver of toxicosis and that highly cohesive herds may greatly reduce the risk of death in even the most dangerous circumstances. By placing the results in context with existing theories about the utility of herds, we demonstrate that grouping in large herbivores can be an adaptive response to patchily distributed poisonous plants. Lastly, our results hold significant management-relevant insight, both for cattle producers managing grazing in larkspur habitat and in general as a call to reconsider the manifold benefits of herd behavior among domestic herbivores.     

The toxicity and kinetics of larkspur alkaloid,methyllycaconitine, in mice

Larkspur poisoning sporadically kills from 5 to 15% of the cattle on North American mountain rangelands. Of the 40 different diterpenoid larkspur alkaloids, the one that is thought to be responsible for much of the toxicity has been identified as methyllycaconitine (MLA). Little is known of MLA toxicokinetics or excretion. The purpose of this study was to further characterize the clinical effects of MLA toxicity in mice and determine the toxicokinetics of MLA excretion. Eight groups of mice were dosed intravenously with 2.0 mg/kg of BW of MLA, killed, and necropsied at 0, 1, 2, 5,10,15, 30, and 60 min after injection. Treated animals were reluctant to move, trembled, and developed dyspnea, muscular twitches, and convulsions. Within several minutes, the clinical signs abated and behavior slowly returned to normal over approximately 20 min. At necropsy serum, brain, liver, kidney, and skeletal muscle were collected and frozen. Blood and tissues were extracted and analyzed for MLA with HPLC and electron spray mass spectrometry. Blood MLA elimination followed a normal biphasic redistribution and excretion pattern (r = 0.99) with a K of elimination of 0.0376 and half-life of 18.4 min. Other tissues had similar clearance rates. These data indicate the MLA is rapidly distributed and excreted. In mice, the clinical effects of poisoning seem to affect the central nervous system, causing dyspnea and "explosive" muscular twitches and convulsions. Because livestock commonly eat larkspur at subclinical doses, they are likely to have larkspur alkaloids in many tissues. These results suggest that animals exposed to larkspur should rapidly excrete MLA (within several hours) and that the residues in animal tissues are not likely to be a problem if animals are given several days to allow toxin clearance.     

Reassessment of the toxicity of Hypericum perforatum (St John's wort) for cattle

OBJECTIVE: To investigate the clinical effect of administering sufficient Hypericum perforatum to cattle to deliver quadruple the reported oral toxic dose. ANIMALS: Thirty-six yearling Hereford (n = 18) and Angus (n = 18) steers. DESIGN: A series of six experiments was conducted, each using 12 animals in a 2 x 2 factorial design, with two breeds of cattle (Hereford, Angus) and two dose levels of hypericin, 1.5 mg/kg (treated group) and 0 mg/kg (control group). Each set of 12 steers was used in duplicate experiments, with all animals alternated between treated and control groups. PROCEDURES: Treated groups received finely milled H. perforatum administered orally in gelatin capsules to provide 1.5 mg hypericin/kg body weight. All cattle were then exposed to direct sunlight for 5 h per day for 5 successive days. Rectal temperatures were measured immediately before and at the end of each sunlight exposure session. Rectal temperature above 40 degrees C, together with some other clinical sign of hypericin poisoning, was considered indicative of intoxication. RESULTS: No animals developed a rectal temperature above 40 degrees C or other clinical signs of hypericin poisoning. CONCLUSIONS: While the reported bovine oral toxic dose of 3 g dried plant/kg body weight, for flowering stage, presumed narrow leaved biotype, H. perforatum, is probably correct, the corresponding dose for hypericin of 0.37 mg/kg is incorrect. Based on its known concentration in this plant the toxic dose of hypericin for partially pigmented Hereford-cross cattle is estimated at about 10.5 mg/kg body weight and more than this for fully pigmented cattle. This would imply that cattle of the former type should be about three and a half times better protected against H. perforatum toxicity than are unpigmented, wool protected, Merino sheep. Cattle, particularly if fully pigmented, may have a role in grazing management to control H. perforatum.     

Toxicity of pyrrolizidine alkaloids from Riddell groundsel (Senecio riddellii) to cattle

The toxicity of Riddell groundsel (Senecio riddellii) gavaged to calves at a known lethal rate was compared with the toxicity of riddelliine and riddelliine N-oxide, the pyrrolizidine alkaloids isolated from the plant, which were fed by intraruminal infusion. Doses of the alkaloids were adjusted to the amount determined to be in the plant and fed individually and in combination. The relative toxicosis in the calves was measured by clinical signs, serum enzyme changes, survival time to morbidity, and histologic changes. Calves fed Senecio riddellii by gavage for 20 consecutive days to provide 45 mg of total pyrrolizidine alkaloids/kg of body weight/d developed clinical signs and serum enzyme changes typical of seneciosis, with 100% morbidity. However, calves receiving riddelliine at 4.5 mg/kg/d for 20 days had neither serum enzyme changes nor clinical signs of pyrrolizidine alkaloidosis. Calves treated with riddelliine N-oxide (40.5 mg/kg/d), and with riddelliine (4.5 mg/kg/d) and riddelliine N-oxide (40.5 mg/kg/d) in combination, had 100% morbidity, although the latter group had fewer liver lesions. These results establish that the N-oxide form of the alkaloid alone is capable of inducing typical Senecio toxicosis in cattle and that the free base level of the plant cannot be considered to be the sole factor in assessing the toxicity of S riddellii.     

Evaluation of vaccination against methyllycaconitine toxicity in mice

The purpose of this study was to determine whether larkspur toxins conjugated to protein carriers would promote active immunity in mice. Mice were injected with several larkspur toxin-protein conjugates or adjuvant alone to determine whether the resulting immunological response altered animal susceptibility to methyllycaconitine, the major toxic larkspur alkaloid. Although vaccinations increased the calculated lethal dose 50% (LD50) for intravenous methyllycaconitine toxicity, overlapping confidence intervals did not provide evidence of differences between the vaccinated and control groups. In the lycoctonine conjugate (LYC)-vaccinated group, mouse survival was related (P = 0.001) to serum titers for methyllycaconitine doses up to 4.5 mg/kg of body weight. When mice withlow antibody titers were removed from the vaccinated groups in which titer was related to survival, the recalculated LD50 estimates were 20% greater than the LD50 of the control group. However, the 95% confidence intervals of the recalculated LD50 groups overlapped with the control groups. Overall, these results suggest that vaccination altered methyllycaconitine toxicity in mice and that vaccination may be useful in decreasing the effects of larkspur toxins in animals. Additional studies are warranted to continue development of potential larkspur vaccines for livestock.     

The effect of body condition on serum concentrations of two teratogenic alkaloids (anagyrine and ammodendrine) from lupines (Lupinus species) that cause crooked calf disease

Several species of lupine (Lupinus spp.) are toxic to livestock, causing death losses in sheep and cattle but more commonly crooked calf disease in pregnant range cows. The major toxic alkaloids in lupine are of the quinolizidine alkaloid group and include the teratogen anagyrine, which is primarily responsible for crooked calf disease. Lupines also contain teratogenic piperidine alkaloids including ammodendrine. Previous work in sheep has shown that lupine alkaloid clearance may be influenced by the animal's physiological status. Therefore, the purpose of this study was to determine if differences in body condition of cattle would alter the absorption and elimination of anagyrine or ammodendrine given in a single oral dose as Lupinus leucophyllus or Lupinus sulphureus, respectively. Mature non-lactating cows in low body condition (LBC, n = 4) and high body condition (HBC, n = 4) received a single dose of dry ground lupine plant (2.0 g/kg of BW) via oral gavage. Lupinus leucophyllus (anagyrine) was dosed first; then after 21 d the same animals were dosed with L. sulphureus (ammodendrine). Blood samples were taken via jugular venipuncture 0 to 60 h after dosing. Serum anagyrine and ammodendrine concentrations were evaluated. The concentration of anagyrine was greater (P = 0.001) in the HBC group and peaked 2 h after dosing versus 12 h in LBC cows. Similarly for ammodendrine, the alkaloid concentration peaked at 3 h after dosing for the HBC group compared with 6 h for the LBC group (P = 0.001). Area under the curve tended to differ (P 相似文献   

Growth rate and physiology of steers grazing tall fescue inoculated with novel endophytes

Cattle grazing tall fescue (Festuca arundinacea Schreb.) often develop fescue toxicosis. This condition is thought to be caused by ergot alkaloids produced by the endophyte Neotyphodium coenophialum. Endophytes from wild tall fescue plants, which do not produce ergot alkaloids, were transferred into the endophyte-free tall fescue germplasm, HiMag. The novel associations also lacked the ability to produce ergot alkaloids. Our objective was to determine whether cattle grazing these novel endophyte associations showed signs of fescue toxicosis. At the Fayetteville, Arkansas location, tester steers (n = 72) were assigned to one of four pasture treatments: endophyte-free HiMag tall fescue (HiMag-); 'Kentucky-31' tall fescue infected with its native, toxic endophyte (KY+); and two novel endophyte-infected tall fescue associations, HiMag4 and HiMag9. At the Mount Vernon, Missouri location, steers (n = 54) were used to test three of the four cultivars (HiMag9 was not tested). Ergot alkaloid concentrations in the forage of HiMag4 and HiMag9 were low or undetectable. Respiration rate, rectal temperature, ADG, and hair scores were measured during the grazing period. Blood was collected via jugular venipuncture and used for prolactin, aspartate aminotransferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), cholesterol, triglyceride, and creatinine analysis. Weight gains by steers grazing HiMag4 and HiMag9 did not differ from those of steers grazing HiMag-, but were greater than gains (P < 0.05) by steers on the KY+ treatment. Steers grazing KY+ had higher (P < 0.05) respiration rates, rectal temperatures, and hair scores than did steers grazing novel endophyte and HiMag- pastures. Prolactin, ALP, cholesterol, LDH, and triglycerides all were suppressed (P < 0.05) in steers grazing KY+ compared with steers grazing novel endophyte and HiMag- pastures. Steers grazing the novel endophyte tall fescues did not suffer from the decreased weight gains and toxicities associated with fescue toxicosis, resulting in enhanced animal production.     

Alterations in hemograms and serum biochemical analytes of steers after prolonged consumption of endophyte-infected tall fescue

The objective of the current study was to delineate changes that occur in serum analytes and blood cellular elements in cattle that graze endophyte-infested (Neotyphodium coenophialum) tall fescue. Tall fescue is grown on more than 35 million acres (14.2 million ha) of pasture in the United States, and three-fourths of the pastures are infected with the endophyte at a 60% or greater level. Tall fescue toxicosis caused by endophyte-produced ergot alkaloids continues to be the most important grass-related disease in the United States, in terms of economic loss to animal producers. However, the agronomic attributes of tall fescue make it an attractive forage species because of its ability to withstand cool temperatures, drought, poor soil conditions, and intensive defoliation from herbivore species, including insects. Tall fescue toxicosis is a complex disease and the need exists to understand the mechanisms of the toxic effects in order to institute effective, prophylactic control measures. Our group previously reported changes that occur in serum biochemical analytes of cattle that graze endophyte-infected tall fescue. An additional year's worth of data have been added, strengthening and corroborating these data. Consistent and significant changes associated with tall fescue toxicosis during the 3-yr study included decreased serum concentrations of cholesterol, globulin (increased albumin/globulin ratio), prolactin, total protein, and copper. The activity of alanine aminotransferase was decreased in serum, whereas an increase in serum concentrations of creatinine and total bilirubin occurred. The present report also documents comparative hemograms of cattle that grazed endophyte-infected or endophyte-free tall fescue over a prolonged period. The mean erythrocyte counts were increased in cattle that grazed endophyte-infected tall fescue, whereas mean corpuscular hemoglobin and mean corpuscular volume were decreased, as were mean eosinophil counts. Thus, repeatable changes have been identified that occur in serum biochemical and blood cellular values of cattle grazing endophyte-infected tall fescue that will aid in understanding the pathogenesis of the disease. In addition, these consistently altered parameters can be used to assess the effectiveness of potential prophylactic treatments.     

Toxicoses in livestock from the hemlocks (Conium and Cicuta spp.)

The hemlocks, Conium maculatum (poison-hemlock) and Cicuta spp. (waterhemlock), are poisonous plants that cause sizeable losss to the livestock industry. Clinical signs of poisonhemlock toxicosis are similar in all species of livestock and include muscular weakness, incordination, trembling, initial central nervous system stimulation, depression and death from respiratory paralysis. Poison-hemlock also causes skeletal defects in the offspring of cattle, pigs and sheep and cleft palate in pigs when ingested during specific periods of gestation. The primary toxicants in poison-hemlock are coniine and gamma-coniceine. Coniine predominates in mature plants and seed, whereas gamma-coniceine predominates in early growth of the plant. Waterhemlock is the most violently toxic poisonous plant known. The toxicant is cicutoxin, which acts on the central nervous system, causing violent convulsions and death. Clinical signs of poisoning appear within 15 min after ingestion of a lethal dose and include excessive salivation, nervousness, tremors, muscular weakness and convulsive seizures interspersed by intermittent periods of relaxation and a final paralytic seizure resulting in anoxia and death. Elevated activities of lactic dehydrogenase, aspartate aminotransferase and creatine kinase in blood are observed, indicative of muscular damage. Toxicoses from poisonhemlock and waterhemlock generally occur in early spring when both plants emerge before other, more palatable plants begin to grow. All parts of the poison-hemlock plant are toxic. The root or tubers of waterhemlock are toxic; however, experimental evidence concerning the toxicity of other plant parts is inconclusive.     

Thiamin supplementation and the ingestive behavior of beef cattle grazing endophyte-infected tall fescue

Livestock grazing endophyte (Acremonium coenophialum Morgan-Jones and Gams)-infected tall fescue (Festuca arundinacea Schreb.) perform poorly due to tall fescue toxicosis, especially when animals are under heat stress. In order to determine whether thiamin promotes recovery from tall fescue toxicosis, 1 or 0 g of thiamin per day, as mononitrate, was fed orally to adult Angus (Bos taurus) cows (380 +/- 8 kg) grazing either tall fescue pasture with and without endophyte or alfalfa (Medicago sativa L.). A tethered grazing system employing a split-plot design was used to estimate intake and components of ingestive behavior. No significant differences attributable to thiamin supplements were seen in rates of intake and biting, grazing time and intake per bite when cows grazed endophyte-infected tall fescue during the first 4 d of exposure. When cows grazed endophyte-infected (greater than 95%) tall fescue with 2,091 micrograms/g loline alkaloids after 4 d of exposure, the untreated animals ingested herbage dry matter (DM) at 1.19 kg/h, whereas the cows receiving thiamin ate 1.57 kg/h (P less than .05). Cattle achieved these rates of DM intake by forming bites of 1.0 and 1.2 g DM at 24 and 26 bites/min when treated with 0 and 1 g of thiamin per day, respectively. Thiamin supplements had no effect on ingestive behavior of cows grazing endophyte-free tall fescue or alfalfa after exposure to these forages for 4 d. Responses to thiamin generally were greater when cattle grazing endophyte-infected tall fescue were exposed to heat stress. Oral thiamin supplementation may alleviate tall fescue toxicosis of beef cattle during warm weather.