Location: Poisonous Plant Research2017 Annual Report
Objective 1: Develop and implement novel management protocols for establishing improved forage species on sites infested with known poisonous plants to reduce the risk of livestock mortality and morbidity, improve livestock performance, and improve rangeland resiliency and diversity. Specifically, develop science-based guidelines for grazing livestock on rangelands infested with Lupinus, Senecio, Delphinium and swainsonine and selenium-containing plants. Objective 2: Reduce the risks of livestock losses due to variations in quantitative and qualitative differences in toxin accumulation over time and plant species by quantifying the influence of endophytes, climate changes, and genotype on plant toxin accumulation (particularly swainsonine-containing plants and Delphinium and Lupinus species). Objective 3: Enhance feed and food safety by improving risk assessment and diagnosis of plant-induced poisoning to livestock by improving analytical methods for analyzing plant and animal tissues for toxins; measuring toxicokinetics, assessing carcinogenic and genotoxic potential, and identifying toxin metabolites and biomarkers of toxicoses. Objective 4: Develop improved procedures with guidelines for diagnostic and prognostic evaluation to reduce negative impacts of poisonous plants on livestock reproduction and embryo/fetal growth by improving early identification of poisoned animals, predicting poisoning outcomes, and management and treatment options through improved understanding of clinical, morphological and molecular alterations of plant-induced toxicosis. Objective 5: Develop guidelines to aid producers and land managers in making genetic-based herd management decisions to improve livestock performance and safety on grazed rangelands infested with poisonous plants through the use of identified animal genes, physiological pathways, and molecular mechanisms of action that underlie Conium, Cicuta, Delphinium, Lupinus, and Nicotiana, and other neurotoxic plant effects.
Livestock poisoning by plants results in over $503,000,000 lost to the livestock industry annually in the 17 western United States from death losses and abortions alone (Holechek, 2002). Plant poisonings extend worldwide to include 333 million poisonous plant-infested hectares in China and 60 million hectares in the central western region of Brazil, to name a few. There are over 6,000 species of pyrrolizidine alkaloid (PA)-containing plants, and over 350 individual PAs causing diseases in animals and humans have been identified. Economic losses are much larger as significant amounts of nutritious forage are wasted and management costs are increased due to the threat of toxic plant-related livestock losses. The Poisonous Plant Research Laboratory (PPRL) has provided worldwide leadership in poisonous plant research to the livestock industry and consumers including numerous solutions to toxic plant problems using an integrated, interdisciplinary approach (see Figure below). The research team investigates plant poisonings in a systematic matter by identifying the plant, describing the effects in animals, determining the toxin(s) and evaluating the mechanisms of action. The ultimate goal is to develop research-based solutions to reduce livestock losses from toxic plants. There are five coordinated objectives in this project plan providing guidelines for potential genetic-based management. This research will reduce livestock losses from plants and enhance the economic well-being of rural communities, improve rangeland health by combating invasive plant species, and help to provide safe animal products free from potential plant toxins for consumers.
Progress was made on all five objectives and their sub-objectives, all of which fall under National Program 215, Component I, Rangeland Management Systems to Improve Economic Viability and Enhance the Environment. Progress was made on identifying sex differences in susceptibility to larkspur intoxication in Angus cattle. Beef producers in the western United States have reported that replacement heifers are most impacted by toxic larkspur (Delphinium) species. Initial findings have demonstrated that Angus heifer yearlings are over ten times more susceptible to toxic larkspur than Angus steers. These research results confirm field reports from ranchers of poisonings. This suggests that replacement heifers should not be grazed in pastures where toxic larkspur species grow. Beef producers in the western United States have reported that younger animals are most impacted by toxic larkspur species. Preliminary results showed Angus steers have a 20 percent greater tolerance to larkspur compared to yearlings by two years of age. This suggests that older animals have a greater tolerance to larkspur intoxication and with careful management can be better suited to graze in pastures that contain toxic larkspur species. Recent research efforts have demonstrated that great variation may exist in plant population density depending on factors such as climate and locale. Delphinium andersonii is a perennial forb on semi-arid rangelands, and population density is related to cattle deaths. A multi-year study was initiated in 2011 to measure toxicity, plant density and life history of D. andersonii populations in southern Idaho. In 4 out of 7 years, essentially no plants emerged and flowered because of drought conditions. During the 3 years when some plants emerged and flowered, plant densities were 2, 7, and 10 plants per square meter (m2); previous research has shown that plant densities greater than 5 plants/m2 pose a serious threat to grazing cattle. Approximately 8 percent of the marked plants remained dormant for 2-4 years, then emerged when precipitation was favorable. Understanding the life history and weather conditions that promote growth of dense Delphinium andersonii populations will enable livestock producers to better manage risk of cattle deaths. A survey of the toxic compounds in water hemlock has been performed in order to determine the variation in toxicity of different populations of water hemlock. Water hemlock is one of the most toxic plants known. Plant samples were collected from sites in Arizona, Utah, Nevada, Idaho, Wyoming, and Colorado. Initial analyses suggest that there is no difference in the toxicity of water hemlock at the various locations. Additional collections will be made. Further, samples of water hemlock will be collected from multiple sites over the growing season to determine if the toxicity of the plant changes as the plant grows and matures. This information will provide a better understanding of the toxic potential of water hemlock throughout the year as well as a better understanding of the variation in toxicity from locations throughout the western U.S. The plant Ipomoea asarifolia has been shown to cause a tremorgenic syndrome in goats. The tremorgenic compounds in I. asarifolia are reported to be indole diterpenes. The chemical profile of these indole diterpene compounds in I. asarifolia has been characterized. Initial efforts have been made to develop the methods to use a mouse model to study the tremorgenic nature of I. asarifolia. Once the mouse model has been developed and validated, the tremorgenic potential of individual purified indole diterpenes will be evaluated. Noxious annual grasses such as medusahead and ventenata are highly invasive and are displacing native vegetation throughout the western U.S. They result in stands of near monocultures reducing livestock and wildlife grazing capacity by 50 to 80%. Weedy and poisonous forbs, such as lupine, are often all that remain for livestock to graze resulting in increased consumption of poisonous plants. Herbicides with different modes of action are being tested to reduce seed production and to control ventenata and medusahead. Targeted grazing by livestock on herbicide treated ventenata and medusahead is being tested to determine if livestock can be used as a tool to remove the annual grasses and provide a seed bed for revegetation of desirable plant species. Providing alternative forages for livestock can help reduce the consumption of poisonous plants by livestock. Efforts are being conducted in collaboration with a foraging behavioral specialist at Utah State University (USU). Death camas is a bulbous perennial forb that occurs in a variety of habitats and is common in sagebrush foothills throughout the western United States. It starts growth early in the spring (typically one of the first plants to begin growth). The lack of alternative forage at this time can result in increased consumption by livestock and death losses, especially in sheep. Recent formulations of herbicides are being tested to determine their efficacy to control death camas while having minimal impacts on desirable forage. Death camas is also being tested to determine if herbicide application affects toxicity of the plant before it senesces. This information can be used to produce guidelines for managers to determine how to safely graze death camas infested rangelands treated with herbicides and what herbicide can most effectively control death camas. Efforts are being conducted in collaboration with a rangeland extension specialist and weed science specialist at USU. Long-term establishment of a competitive plant community on degraded rangelands within the arid Intermountain west is necessary to compete with invasive and/or poisonous plants. Broom snakeweed increases following disturbances such as overgrazing, drought, or wildfire and is toxic to livestock. Establishing a competitive plant community can help reduce the establishment and spread of broom snakeweed. Long-term monitoring is being conducted on research plots that were seeded in 2003 to determine if native and introduced grasses can persist in the arid environment of the Intermountain west and if the seeded species will provide competition to reduce poisonous plants. Efforts are being conducted in collaboration with a rangeland extension specialist at USU. Dehydropyrrolizidine alkaloids (PAs) are plant toxins that can poison livestock, wildlife and humans. Several have also been shown to be carcinogens. T demonstrated that riddelliine induced neoplasms at increased incidences regardless of dose or exposure duration. This work was important as it indicated that any PA exposure can increase the incidence of PA-related carcinogenesis. We have also shown the PAs, lasiocarpine, seneciophylline, senecionine and heliotridine were more toxic than riddelliine and thus potentially more carcinogenic. To further evaluate this hypothesis we have generated a colony of knockout mice and initiated studies to directly compare the carcinogenicity of these purified PAs. Additionally, we have further developed techniques to identify PA metabolites or adducts from livers and tissues of animals that were exposed to PAs by comparing adducts from tissues from cattle, horses, pigs and rodents. Initial results suggest the improved techniques will enhance detection of PA exposure and estimating initial dose and when used with histologic studies might be used to predict disease course and prognosis. Selenium concentration in forage may negatively impact reproduction in livestock. Bulls were fed alfalfa pellets containing selenium concentrations to mimic concentrations found in forages on some seleniferous soils. High levels of selenium in the diet had no effect on sperm motility or morphology. However, high selenium caused lameness and/or congestive heart failure in some animals after 12 weeks of feeding the high selenium alfalfa pellets. These results suggest that cattle producers grazing in regions where forages are high in selenium should manage their herds to avoid exposure to high selenium forages for prolonged periods. Certain lupine (Lupinus) species in the western United States cause crooked calf syndrome (CCS). One alkaloid in particular, anagyrine, is very problematic in cattle and has been proposed to be metabolized to a teratogenic alkaloid that inhibits fetal movement, the putative mechanism behind CCS. In this cell culture research using two cell lines, an alternative hypothesis that anagyrine directly desensitizes fetal muscle was tested. Research results indicate that anagyrine is bioactive without metabolism and is directly a factor that causes malformation of an embryo (teratogenic) in cattle. Because un-metabolized anagyrine is bioactive, it can be used as a biomarker for the selection of cattle resistant to the teratogenic actions of quinolizidine alkaloids found in lupines. Soils high in selenium may promote the growth of toxic, high selenium forage. High selenium soil was treated with various amendments that could be used on reclaimed mine sites where poisonous selenium-accumulating forages grow. The addition of iron as an amendment to high selenium soil resulted in approximately a 90 percent decrease in the uptake of selenium by western aster, intermediate wheat grass, and alfalfa. The addition of the iron amendment also resulted in an increase in the biomass of intermediate wheat grass and alfalfa while decreasing the biomass of the highly toxic western aster. The information obtained in this study indicates iron can be used as an amendment to decrease selenium concentrations in forages growing on selenium-contaminated reclaimed mine sites.
1. Liver toxicity of Salvia compounds in cattle. ARS scientists in Logan, Utah, investigated a field case of cattle poisoning in Colorado where 170 cows in a herd of over 500 died after eating weed-infested alfalfa hay. Several hepatotoxic diterpenes were isolated from the contaminated alfalfa hay fed to the deceased animals. A bioassay guided chemical fractionation and extraction process to identify the toxins of the weedy hay was used. The identified diterpenoids known to be present in different Salvia species led to the identification of dried plant parts (stem and flower pods) of the toxic plant in bales of hay. A reexamination of the hay field location found a significant population of the toxic Salvia along the hay field edges and irrigation ditch banks. Historically, Salvia species have been suspected of causing toxicity in several areas worldwide, but this research is the first to link the diterpene compounds in Salvia with liver toxicity in livestock and will provide important information to veterinarians for diagnosis, and to livestock and hay producers to prevent poisonings in the future.
2. Effects of elevated carbon dioxide (CO2) on two Astragalus species. Understanding how locoweed responds to elevated CO2 is important for risk assessment as the climate changes. ARS researchers in Logan, Utah, in collaboration with other scientists, evaluated how two Astragalus species responded to elevated CO2 in a controlled environment. Swainsonine concentrations were not strongly affected by elevated CO2. Other traits such as biomass and water soluble carbohydrates responded positively while crude protein responded negatively to elevated CO2. Information on how toxic plants and their toxic principles respond to climate change is essential to risk assessment.
3. Rangeland restoration in central Washington to reduce losses from lupine-induced crooked calf syndrome (CCS). Lupine-induced crooked calf syndrome has caused devastating losses to cattle ranchers in central Washington, which may be exacerbated by declining forage conditions on rangelands due to invasive annual weeds. ARS Scientists at Logan, Utah, completed a three year analysis funded by a Western Sustainable Agriculture Research and Education (SARE) grant (OW13-005) to study the impacts of seeding rangelands infested with toxic lupine species. Results showed that degraded rangeland, heavily infested with undesirable plants such as cheatgrass and medusahead rye as well as lupine, could be substantially restored using targeted grazing followed by seeding with perennial grasses and forage Kochia. Improved rangeland conditions will reduce the need for cattle to graze lupine and other poisonous plants present on these ranges. More desirable forage production will improve cattle production in this region, including a reduction in CCS losses from lupines.
4. Detection of pyrrolizidine alkaloids in herbal products. ARS scientists in Logan, Utah, in cooperation with American Herbal Pharmacopoeia, analyzed about 70 samples, purported to be from the herbal plant “boneset” (Eupatorium perfoliatum), for the presence of dehydropyrrolizidine alkaloids. These alkaloids are potentially toxic, associated with liver and lung damage, congenital anomalies and various cancers. The results clearly show that “boneset” contains toxic dehydropyrrolizidine alkaloids. Further, there is misidentification of plants by some collectors, revealed by the difference in the alkaloids detected. Tinctures and water infusions of “boneset” also contain the alkaloids. Pyrrolizidine alkaloids are present in many herbal products, and potentially serious negative impacts on human heath, particularly liver toxicity. These findings will provide valuable information to the herbal products industry and consumer to reduce safety concerns and toxicity problems in humans.
5. Swainsonine biosynthesis genes in diverse symbiotic and pathogenic fungi. Understanding the genes responsible for swainsonine biosynthesis provides fundamental knowledge that may provide a means to render swainsonine-containing plants less toxic. ARS researchers in Logan, Utah, in collaboration with other scientists, identified the gene cluster responsible for swainsonine biosynthesis in two endophytes associated with two families of swainsonine-containing plants. This research extended the breadth of swainsonine-producing fungi to include human and other mammalian pathogens. Understanding swainsonine biosynthesis may provide critical knowledge to ultimately alter swainsonine production thus rendering plants less toxic.
6. Switchgrass pellets used as horse bedding material. Switchgrass (Panicum virgatum) is grown and harvested for biofuel, and switchgrass straw is used to make bedding pellets for livestock, but the material contains saponins. Saponins have been implicated in photosensitization in livestock, including horses. ARS scientists in Logan, Utah, examined the saponin concentration in switchgrass straw, and in bedding pellets made from switchgrass straw. It was determined the palatability of bedding pellets made from switchgrass straw to horses. Switchgrass straw and bedding pellets made from switchgrass straw contained low concentrations of saponins, however, horses still rejected eating switchgrass bedding pellets. These results indicate that the risk of intoxication from horses ingesting bedding pellets made with switchgrass straw is very low, or non-existent, and is important knowledge for commercial pellet makers and horse owners.
7. Consumption of larkspur by resistant and susceptible cattle. Larkspurs are a major cause of cattle losses on western ranges in North America, especially on foothill and mountain rangelands. ARS scientists at Logan, Utah, screened cattle to provide groups of resistant and susceptible animals. Cattle grazed for several seasons on a larkspur-infested rangeland in southeastern Idaho. Susceptible animals initially consumed more larkspur than did resistant animals, provoking serious and potentially fatal intoxication in susceptible animals. However, by the end of the grazing seasons, there were few differences in larkspur consumption between resistant and susceptible cattle. Resistant cattle may consume 2-3 times the amount of larkspur that susceptible animals consume with greatly reduced incidences of overt poisoning and death which is important to livestock producers who graze animals where larkspurs are an important component of the vegetation.
8. Identification of tremorgenic compounds in Ipomoea asarifolia and Ipomoea muelleri. I. asarifolia and I. muelleri have been associated with a tremorgenic syndrome in livestock in Brazil and Australia, respectively. ARS scientists at Logan, Utah, characterized the tremorgenic compounds in I. asarifolia and I. muelleri by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. This is the first detailed mass spectrometry analysis of the tremorgenic compounds in I. asarifolia and I. muelleri. These analytical methods will be important for determining the toxin concentration in plants and thus the toxic risks associated with individual plant populations.
9. Development of a gas chromatography-mass spectrometry (GC-MS) method for the analysis of monofluoroacetate in plants toxic to livestock. Monofluoroacetate is a potent toxin that occurs in over 50 plant species in Africa, Australia, and South America. It is responsible for significant livestock deaths in these regions. For example, monofluoroacetate containing plants are responsible for >50% of livestock losses in Brazil (>500,000 cattle annually). ARS scientists at Logan, Utah, developed a quantitative method for the analysis of monofluoroacetate in plants. Monofluoroacetate was detected in the following plants for the first time: Fridericia elegans, Niedenzuella multiglandulosa, Niedenzuella acutifolia, and Aenigmatanthera lasiandra. This method is another tool to mitigate livestock poisoning by monofluoroacetate-containing plants by increasing the ability of scientists to evaluate the poisoning risk of these plants.
10. A survey of North American Astragalus plant populations for swainsonine (the locoweed toxin). A systematic examination for swainsonine in these species provided a definitive reference in regard to species containing swainsonine and is a valuable reference for land managers. ARS researchers in Logan, Utah, conducted a systematic examination for swainsonine in multiple Astragalus species. Fifty-two Astragalus species were screened for swainsonine using chemical analytical techniques. Swainsonine was detected in twenty-nine species previously not reported to contain swainsonine. The expanded list of swainsonine-containing taxa will serve as an essential reference for risk assessment and avoidance of livestock poisoning on rangelands with Astragalus species.
11. The role of calystegines from Ipomoea carnea in poisoning goats. Swainsonine is a potent toxin found in numerous plant species around the world, including several types of locoweeds found in the United States. I. carnea contains swainsonine and calystegines (a similar toxin). ARS scientists in Logan, Utah, in cooperation with Brazilian scientists, evaluated the role of calystegines in goats poisoned by I. carnea. They determined that when locoweed (Astragalus) and I. carnea are fed to goats at equal swainsonine doses that there is minimal differences between the goats dosed with the two plants. These research results indicate that the Ipomoea produced calystegines contribute little to the development of Ipomoea-induced neurologic disease, rather swainsonine is the critical toxin in I. carnea.
12. The effect of ponderosa pine needles on the rumen microbiome of cattle. Consumption of ponderosa pine needles by cattle during the later stages of pregnancy can cause abortions to occur. Previous research by ARS scientists in Logan, Utah, demonstrated that there is a difference in metabolism of the compounds in the pine needles that cause abortions between cattle that are naïve to ponderosa pine needles versus cattle that have been conditioned (i.e., exposed) to the pine needles. Recent results have now shown that rumen microbe populations change upon exposure to pine needles, which alters the metabolism of the compounds causing the abortions. However, the change is very transitory as the microbe populations revert back to baseline within one week after pine needle exposure stops. This data provides important knowledge regarding adaption of cattle to poisonous plants and the feasibility of potential preventative treatments.
13. Characterization of absorption and elimination of larkspur alkaloids in goats dosed orally versus intravenously. Larkspur (Delphinium) plants are acutely toxic to cattle, resulting in significant cattle losses every year. ARS scientists in Logan, Utah, compared the absorption and elimination of the toxic compounds in larkspur plants in goats that were dosed both orally and intravenously (IV). It was determined that the absorption of the toxins is the rate limiting step in the kinetic process. This knowledge will help provide a better understanding of how and when to treat cattle that have been poisoned by larkspur.
14. The effect of multiple doses of a less toxic larkspur plant to cattle. Larkspur (Delphinium) plants are acutely toxic to cattle, resulting in significant cattle losses every year. However, different species of larkspur, and even different populations of a given species of larkspur, have different toxic risks. In order to more fully characterize the toxic potential of larkspurs, ARS scientists in Logan, Utah, dosed cattle with a less toxic larkspur twice a day for four days. It was determined that the cattle can become poisoned when dosed with a less toxic larkspur multiple times in a short time period. This knowledge will help in defining the risk of poisoning for all larkspur plants, whether they are highly toxic or less toxic.
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