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ARS Home » Pacific West Area » Logan, Utah » Poisonous Plant Research » Research » Research Project #424163

Research Project: Understanding and Mitigating the Adverse Effects of Poisonous Plants on Livestock Production Systems

Location: Poisonous Plant Research

2018 Annual Report


Objectives
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.


Approach
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 Report
This is the final report for this project which was bridged by 2080-32630-013-00D, “Understanding and Mitigating the Adverse Effects of Poisonous Plants on Livestock Production Systems”, in January 2018, while peer panel review of the next five-year project plan is undergoing assessment by the Office of Scientific Quality Review. For additional information, see the report for the bridging project. Progress was made on all five Objectives and their Sub-objectives, all of which fall under National Program 215, Component I, Improved Rangeland Management for Enhanced Livestock Production, Conservation and Ecological Services. Progress on this project focuses on Problem A, the need for developing economic livestock grazing systems for rangelands that meet global food security objectives while being adaptable to changing climate and varying environmental conditions and preserve the natural resources integrity. Results have been communicated through peer-reviewed publications and to stakeholders through various means. Objective 1: Grass and forb species were identified that improve range conditions by increasing the quantity and quality of other available forage, thus reducing the risk of livestock poisoning by plants. It was found that changes in livestock reproductive capacity and production efficiency were negatively affected because of chronic, low-dose selenium intake. Progress to determine the weather factors that influence the population dynamics and alkaloid composition of Delphinium andersonii was made. Objective 2: It was determined that the concentrations of abortifacient labdane acids in western juniper vary among different locations and over time. Fungicide application and clipping do not alter swainsonine concentrations or the transmission of the endophyte. Swainsonine concentrations in locoweeds are not influenced by elevated carbon dioxide (CO2) but other measures like biomass and crude protein change as a result of elevated CO2. The alkaloid composition of other Delphinium species, including D. stachydeum and D. ramosum was determined. Swainsonine was identified in several North and South American Astragalus species, previously not known to contain it, Oxytropis species from North America, and Swainsona species from Australia. The gene cluster responsible for swainsonine biosynthesis in endophytes and other fungi that are reported to contain swainsonine was identified. Objective 3: The comparative toxicity of the different forms of selenium in plants and their toxicokinetics and pathology in sheep and cattle were identified and characterized. It was demonstrated that the putative toxin tremetone is likely not responsible solely for the toxicity of rayless goldenrod and white snakeroot. A polymerase chain reaction (PCR)-based method was developed to detect poisonous plants like larkspur in mixed feeds and the gastrointestinal contents of poisoned animals. The toxicity and carcinogenic potential of pyrrolizidine alkaloids (PAs) like riddelliine and their metabolites were identified and characterized. Methods were developed for the detection of toxic metabolites (pyrroles) in liver samples from animals poisoned with pyrrolizidine alkaloids. Progress was made in the identification of the major diterpene acids in broom snakeweed and their rumen and sera metabolites. Methods were developed to detect metabolites of ponderosa pine identified from the sera of poisoned animals in fetal tissues from diagnostic cases, and methods were developed for the detection and quantitation of toxic principles including monofluoroacetate. Objective 4: Species susceptibility to locoweed poisoning and other swainsonine-containing plants (Ipomoea carnea) was described and compared. The effects of western juniper trees on cattle reproduction was characterized and management guidelines to reduce losses from abortions due to ponderosa pine and related species were further refined. The teratogenic potential of piperidine and quinolizidine alkaloids in cell culture, rodent, and goat models was evaluated to calculate the relative risk of each alkaloid for causing fetal deformities. The abortifacient effects of western juniper were characterized. It was found that pre-conditioned and naïve cattle metabolize the abortifacient compounds from ponderosa pine differently and that the serum toxicokinetics of larkspur toxins differs among cattle, sheep and goats. Livestock exposed to multiple toxins from different toxic plants may not be at greater risk if the toxins affect different body systems. The effects of larkspur in cattle ingesting the plant over several days to simulate natural grazing conditions was characterized. It was found that the rumen microbiome changes with ingestion of ponderosa pine in cattle. Objective 5: It was found that cattle within and between breeds may differ greatly in resistance or susceptibility to Delphinium alkaloids, and that differences in response may be genetic and heritable. ARS researchers characterized the physiologic and toxicokinetic effects of varying dose, duration, and frequency of toxic plant alkaloids in livestock including larkspur where the clearance time (half-life) for the major toxic alkaloid in Delphinium was 20 hours. The biological mechanisms of action of several piperidine and quinolizidine alkaloids that may or not be teratogenic were also characterized.


Accomplishments
1. Two Delphinium ramosum chemotypes, their biogeography and potential toxicity. Larkspurs (Delphinium, Ranunculaceae) are poisonous plants found on rangelands throughout western North America. Two main structural groups of norditerpene alkaloids, the N-(methylsuccinimido) anthranoyllycoctonine type (MSAL-type) and the non-MSAL type, are responsible for larkspur-induced poisoning. Information on the alkaloid composition is lacking for several Delphinium species, including D. ramosum, which grows throughout parts of Colorado and northern New Mexico. ARS scientists in Logan, Utah, investigated the alkaloid composition of D. ramosum throughout its geographical distribution using both field and herbarium specimens. They identified two alkaloid profiles and found that each had a unique geographical distribution. One profile contained significantly greater concentrations of the MSAL-type alkaloids than the other. This information has important implications in grazing management decisions on D. ramosum-infested rangelands and demonstrates that botanical classification alone is not a fully adequate indicator of relative risk of toxicity.

2. Selenium (Se) concentrations in plants and soil. Selenium concentrations in western aster (Symphyotrichum ascendens Lindl.) are dependent upon Se species and concentrations in Se-contaminated soil. Selenium accumulation in vegetation has resulted in poisoning of livestock that graze on historic phosphate mine soils in southeastern Idaho. ARS scientists in Logan, Utah, demonstrated that soluble and phosphate-extractable Se (selenite and selenate) were determined to be “bioavailable fractions” for western aster. Thus, simple water extractions can be used for quick assessment of Se bioavailability to western aster and provide a means to identify potentially hazardous areas. This information is helpful to regulatory agencies and mining officials when determining the potential risk of grazing livestock on reclaimed mining areas.

3. Cell culture investigations of teratogenic compounds. Are cell culture studies alone an accurate predictor of the ability of toxins to cause birth defects in livestock? ARS scientists from Logan, Utah, compared different piperidine alkaloid toxins from poisonous plants and their effects on neurological receptors. Specialized cell lines (TE-671 and SHSY-5Y cells) and pregnant goats were used to characterize the mechanism and increase understanding of why these plants cause birth defects and animal deaths. Results suggest that, while experiments with isolated cells provide valuable information and predictions of the actions of plant alkaloids, animal experiments are still required to determine the ability of an alkaloid to inhibit fetal movement in livestock species. Moreover, other pharmacological properties such as receptor differences between mammalian species and differences in the toxicological properties of the alkaloids are also likely to weaken teratologic predictions based solely on the cell culture data.

4. Fungicide treatment and clipping of locoweed (Oxytropis sericea) does not disrupt swainsonine concentrations. Swainsonine, an indolizidine alkaloid, is an a-mannosidase and mannosidase II inhibitor that causes significant livestock losses via lysosomal storage disease and altered glycoprotein processing. Swainsonine is found in several plant species worldwide and prolonged consumption of these plants by livestock causes a disease condition characterized by weight loss, depression, altered behavior, decreased libido, infertility, and death. ARS scientists in Logan, Utah, tested the hypothesis that fungicide application and clipping of plant vegetative tissues may alter swainsonine concentrations, thus rendering the plant less toxic. Plants were treated with four different fungicides and clipped to determine if swainsonine concentrations were altered. Treatment of Oxytropis sericea with any of four different fungicides did not alter swainsonine concentrations in plants at any of three harvest timings. These results demonstrate that clipping and fungicide treatment are not options that will render locoweeds less toxic and should not be pursued.

5. Analysis of monofluoroacetate in plants toxic to livestock and in rumen contents as a diagnostic tool. Monofluoroacetate is a potent toxin that occurs in several species in four plant families that may occur in Africa, Australia, and South America and is responsible for significant livestock deaths in these regions. ARS scientists in Logan, Utah, using different analytical methods detected monofluoroacetate in the South American plants Fridericia elegans, Niedenzuella multiglandulosa, Niendenzuella acutifolia, and Aenigmatanthera lasiandra. Monofluoroacetate was also detected in the rumen contents of sheep poisoned in Australia by Gastrolobium species. This is the first report of monofluoroacetate being detected in these plants, some of which have been reported to cause sudden death or toxicity in livestock. More importantly, this is the first time that monofluoroacetate has been detected in the rumen contents of a poisoned animal. Methods developed for the detection of monofluoroacetate may be used as tools to identify plants that pose a toxic risk to livestock as well as in diagnostic investigations of infected livestock.

6. Identification of pyrrolizidine alkaloids in various Senecio species from Uruguay. Senecio is a genus of the daisy family that includes ragworts and groundsels. Samples of several Senecio species were surveyed by an ARS scientist in Logan, Utah, in collaboration with scientists from Uruguay, for the potentially toxic compounds known as pyrrolizidine alkaloids (PAs). PAs are potent liver toxins that, under some conditions, can be carcinogenic. PAs were detected in these species and found to be unique to each type. The results provide tools for land managers in Uruguay to make better grazing management decisions due to the toxic risk of Senecio.

7. A survey of swainsonine content in Swainsona species. Swainsonine, an indolizidine alkaloid, is found in several plant species worldwide, and causes severe toxicosis when ingested by livestock. Some species of the Australian genus Swainsona have been reported to be toxic to livestock due to the toxin swainsonine but a systematic screen using modern chemical instrumentation is lacking. Swainsonine was detected by ARS scientists in Logan, Utah, and an Australian collaborator using both liquid chromatography-mass spectrometry (LCMS) and gas chromatography-mass spectrometry (GCMS). Nine of 41 species screened tested positive where 8 of them had been previously determined as negative for swainsonine. Herbarium specimens were collected to assist in identification. This data set provides a valuable tool for risk assessment and diagnostic purposes and highlights the utility of herbarium specimens in phytochemical studies.


Review Publications
Cook, D., Gardner, D.R., Lee, S.T., Stonecipher, C.A., Pfister, J.A., Welch, K.D., Green, B.T. 2017. Two Delphinium ramosum chemotypes, their biogeographical distribution and potential toxicity. Biochemical Systematics and Ecology. 75:1-9. https://doi.org/10.1016/j.bse.2017.09.002.
Green, B.T., Lee, S.T., Keele, J.W., Welch, K.D., Cook, D., Pfister, J.A., Kem, W.R. 2018. Complete inhibition of fetal movement in the day 40 pregnant goat model by the piperidine alkaloid anabasine but not related alkaloids. Toxicon. 144:61-67. https://doi.org/10.1016/j.toxicon.2018.02.007.
Welch, K.D., Lee, S.T., Davis, T.Z. 2017. An evaluation of the toxicity of white snakeroot (Ageratina altissima) and rayless goldenrod (Isocoma pluriflora) in a lactating mouse model. International Journal of Poisonous Plant Research. 4(1):43-52. Available: https://www.ars.usda.gov/oc/np/poisonousplants/poisonousplantresearchjournalintro/
Lee, S.T., Davis, T.Z., Cook, D. 2017. Evaluation of the stability of benzofuran ketones in rayless goldenrod (Isocoma pluriflora) and white snakeroot (Ageratina altissima) under different storage conditions. International Journal of Poisonous Plant Research. 4(1):36-42.
Caldeira, F.H., Arruda, F.P., Shenkel, D.M., Marcolong-Pereira, C., Lee, S.T., Cook, D., Riet-Correa, F., Colodel, E.M. 2017. Intoxicação experimental por Niedenzuella stannea (Malpighiaceae) em ovinos. Pesquisa Veterinaria Brasileira. 37(7):681-685. https://doi.org/10.1590/S0100-736X2017000700005.
Panter, K.E., Taylor, J.B., Lee, S.T., Strong, N.K., Wierenga, T.L., Cook, D., Welsh, S.L. 2017. Lupine poisoning in sheep on the USDA-ARS U.S. Sheep Experiment Station (USSES), Dubois, Idaho. International Journal of Poisonous Plant Research. 4:79-87.
Colegate, S.M., Gardner, D.R., Resager, W.C., Bollar, N., Betz, J.M., Panter, K.E. 2017. Hydroxylic solvent-induced ring opening of the dehydropyrrolizidine alkaloids riddelliine and seneciphylline: Implications for toxicity and analytical studies. International Journal of Poisonous Plant Research. 4:1-15.
Butler, R., Tai, S., Allen, J.G., Cook, D., Lee, S.T. 2017. Gastrolobium spp. poisoning in sheep: A case report. International Journal of Poisonous Plant Research. 4:68-71.
Panter, K.E., Colegate, S.M., Davis, T.Z., Welsh, S.L., Gardner, D.R., Cuneo, P.S., Stegelmeier, B.L., Stonecipher, C.A. 2017. Fiddleneck (Amsinckia intermedia Lehmann Boraginaceae): Toxicity in cattle potentiated by burrow weed (Isocoma acradenia). International Journal of Poisonous Plant Research. 4(1):16-24.
Welsh, S.L., Panter, K.E., Colegate, S.M., Gardner, D.R., Cuneo, P.S., Davis, T.Z., Stegelmeier, B.L., Stonecipher, C.A. 2017. Amsinckia Lehmann (Boraginaceae): A summary taxonomic review. International Journal of Poisonous Plant Research. 4(1):25-35.
Lee, S.T., Gardner, D.R., Cook, D. 2017. Identification of indole diterpenes in Ipomoea asarifolia and Ipomoea muelleri, plants tremorgenic to livestock. Journal of Agricultural and Food Chemistry. 65:5266-5277. https://doi.org/10.1021/acs.jafc.7b01834.
Alhawatema, M.S., Gebril, S., Cook, D., Creamer, R. 2017. RNAi-mediated down-regulation of a melanin polyketide synthase (pks1) gene in the fungus Slafractonia leguminicola. World Journal of Microbiology and Biotechnology. 33(10):179. https://doi.org/10.1007/s11274-017-2346-y.
de Oliveira Neto, T.S., Riet-Correa, F., Lee, S.T., Cook, D., Sousa Barbosa, F.M., da Silva Neto, J.F., Simões, S.V., Lucena, R.B. 2017. Poisoning in goats by the monofluoracetate-containing plant Palicourea aeneofusca (Rubiaceae). Toxicon. 135:12-16. https://doi.org/10.1016/j.toxicon.2017.05.025.
Pimentel, L.A., Maia, L.A., Campos, E.M., Dantas, A.F., Medeiros, R.M., Pfister, J.A., Cook, D., Riet-Correa, F. 2012. Conditioned food aversion to control outbreaks of intoxication by Ipomoea carnea and Turbina cordata in goats. Pesquisa Veterinaria Brasileira. 32(8):707-714. http://dx.doi.org/10.1590/S0100-736X2012000800005.
Stegelmeier, B.L. 2016. Overview of sweet clover poisoning. In: Aiello, S.E., Moses, M.A, editors. Merck Veterinary Manual. 11th edition. Kenilworth, NJ: Merck and Company. Available: https://www.merckvetmanual.com/SearchResults?query=sweet+clover+poisoning.
Stegelmeier, B.L. 2016. Overview of bracken fern poisoning. In: Aiello S.E., Moses, M.A, editors. Merck Veterinary Manual. 11th edition. Kenilworth, NJ: Merck and Company. Available: https://www.merckvetmanual.com/SearchResults?query=bracken+fern+poisoning.
Pfister, J.A., Villalba, J., Gardner, D.R. 2012. Effect of dietary protein level and quebracho tannin on consumption of pine needles (Pinus ponderosa) by beef cows. Professional Animal Scientist. 28(5):528-533. https://doi.org/10.15232/S1080-7446(15)30401-0.
Gotardo, A.T., Schumaher, B.H., Pfister, J.A., Traldi, A.S., Maiorka, P.C., Spinosa, H.S., Gorniak, S.L. 2012. The use of ultrasonography to study teratogenicity in ruminants: Evaluation of Ipomoea carnea in goats. Birth Defects Research Part B: Developmental and Reproductive Toxicology. 95(4):289-295. https://doi.org/10.1002/bdrb.21017.
Estep, A.S., Becnel, J.J., Lee, S.T. 2016. Toxicity of compounds isolated from white snakeroot (Ageratina altissima) to adult and larval yellow fever mosquitoes (Aedes aegypti). Natural Product Communications. 11(11):1675-1677.
Clemensen, A.K., Rottinghaus, G.E., Lee, S.T., Provenza, F.D., Villalba, J.J. 2017. How planting configuration influences plant secondary metabolites and total N in tall fescue (Festuca arundinacea Schreb.), alfalfa (Medicago sativa L.) and birdsfoot trefoil (Lotus corniculatus L.). Grass and Forage Science. 1-7. https://doi.org/10.1111/gfs.12298.
Favorito, J.E., Eick, M.J., Grossl, P.R., Davis, T.Z. 2017. Selenium geochemistry in reclaimed phosphate mine soils and its relationship with plant bioavailability. Plant and Soil. 418(1-2):541-555. https://doi.org/10.1007/s11104-017-3299-5.
Panter, K.E., Welch, K.D., Gardner, D.R. 2014. Poisonous plants: Biomarkers for diagnosis. In: Gupta, R.C., editor. Biomarkers in Toxicology. Oxford, UK: Elsevier. p. 563-589. https://doi.org/10.1016/C2012-0-01373-7.
Santos-Barbosa, J.M., Lee, S.T., Cook, D., Gardner, D.R., Viana, L.H., Re, N. 2017. A gas chromatography-mass spectrometry (GC-MS) method for the detection and quantitation of monofluoroacetate in plants toxic to livestock. Journal of Agricultural and Food Chemistry. 65(7):1428–1433. https://doi.org/10.1021/acs.jafc.7b00294.
Cook, D., Gardner, D.R., Roper, J.M., Ransom, C.V., Pfister, J.A., Panter, K.E. 2016. Fungicide treatment and clipping of Oxytropis sericea does not disrupt swainsonine concentrations. Toxins. 122:26-30. https://doi.org/10.1016/j.toxicon.2016.09.012.
Cook, D., Gardner, D.R., Welch, K.D., Allen, J.G. 2017. A survey of swainsonine content in Swainsona species. The Australian Rangeland Journal. 39:213-218. https://doi.org/10.1071/RJ16088.
Cook, D., Gardner, D.R., Pfister, J.A., Lee, S.T., Welch, K.D., Welsh, S.L. 2017. A screen for Swainsonine in select North American Astragalus species. Chemistry and Biodiversity. 14(4):e1600364. https://doi.org/10.1002/cbdv.201600364.
Cook, D., Donzelli, B., Creamer, R., Baucom, D.L., Gardner, D.R., Pan, J., Moore, N., Krasnoff, S., Jaromczyk, J.W., Schardl, C.L. 2017. Swainsonine biosynthesis genes in diverse symbiotic and pathogenic fungi. G3, Genes/Genomes/Genetics. 7(6):1791-1797. https://doi.org/10.1534/g3.117.041384.
Peixoto De Arruda, F., Bravim Caldeira, F.H., Ducatti, K., Bezerra, K.S., Marcolongo-Pereira, C., Lee, S.T., Cook, D., Riet-Correa, F., Colodel, E. 2017. Experimental poisoning by Niedenzuella stannea in cattle and corresponding detection of monofluoroacetate. Ciencia Rural. 47(03):e20160761. http://dx.doi.org/10.1590/0103-8478cr20160761.
Stegelmeier, B.L., Brown, A.W., Welch, K.D. 2015. Safety concerns of herbal products and traditional Chinese herbal medicines: Dehydropyrrolizidine alkaloids and aristolochic acid. Journal of Applied Toxicology. 35(12):1433-1437. https://doi.org/10.1002/jat.3192.
Pfister, J.A., Lee, S.T., Arnett, D., Panter, K.E. 2017. Preference by horses for bedding pellets made from switchgrass (Panicum virgatum) straw. Professional Animal Scientist. 33(3):349–356. https://doi.org/10.15232/pas.2016-01585.
Clemensen, A.K., Provenza, F.D., Lee, S.T., Gardner, D.R., Rottinghaus, G.E., Villalba, J.J. 2017. Plant secondary metabolites in alfalfa, birdsfoot trefoil, reed canarygrass, and tall fescue unaffected by two different nitrogen sources. Crop Science. 57(2):964–970. https://doi.org/10.2135/cropsci2016.08.0680.
Preliasco, M., Gardner, D.R., Moraes, J., Gonzalez, A.C., Uriarte, G., Rivero, R. 2017. Senecio grisebachii Baker: Pyrrolizidine alkaloids and experimental poisoning in calves. Toxicon. 133:68-73. https://doi.org/10.1016/j.toxicon.2017.05.004.
Riet-Correa, F., Medeiros, R.M., Pfister, J.A., Mendonça, F.S. 2017. Toxic plants affecting the nervous system of ruminants and horses in Brazil. Pesquisa Veterinaria Brasileira. 37(12):1357-1368. http://dx.doi.org/10.1590/s0100-736x2017001200001.