Progress 01/31/18 to 02/24/19
Outputs
Progress Report Objectives (from AD-416): 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 (from AD-416): 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 Unit (PPRU) 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. 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. This was a final report for this bridging project, which began in January 2018 and expired in February 2019. This project is replaced with 2080- 32630-014-00D, "Understanding and Mitigating the Adverse Effects of Poisonous Plants on Livestock Production Systems." For additional information, see the new project report. Different herbicides to aid in the establishment of newly seeded grass species in revegetated rangelands infested with annual grasses that also contain populations of poisonous plants such as lupines were evaluated. How different toxins change in various toxic plants as a function of plant phenology was investigated. Diverse species of several different genera (Delphinium, Astragalus) were screened for their associated toxic principles to assess toxic risk. Different non-invasive specimens to aid in diagnostic investigations were evaluated. Animal-specific factors such as age and how these factors influence an animal⿿s relative susceptibility to toxic plants, such as larkspur, were assessed. Research to identify genetic markers that may explain differences in animal susceptibility due to poisonous plants, such as larkspur, was continued. Angus cattle differing in susceptibility to larkspur poisoning were used to assess selection of duncecap larkspur (Delphinium occidentale) while grazing. ARS scientists monitored diet selection of 12 cattle (6 susceptible, 6 resistant) over a grazing period for three summers. The only fatalities (2) were in susceptible animals. Selecting resistant cattle to graze larkspur-infested rangelands may reduce losses; however, further research is required to develop genetic biomarkers to identify such animals. Accomplishments 01 Development of a model to study plant-induced muscle tremors. Ipomoea asarifolia has been associated with a tremorgenic syndrome which causes muscle tremors in livestock. ARS scientists in Logan, Utah, assessed the tremorgenic nature of Ipomoea asarifolia using a mouse model. Results from this study demonstrate that the tremorgenic compounds in Ipomoea asarifolia are endophyte derived. Additionally, both adult mice and nursing pups are good models for studying the tremorgenic nature of Ipomoea asarifolia and related plants. This work demonstrated that a mouse model can be used to assess the tremorgenic nature of plants, as well as the purified compounds, which will be helpful in fully identifying the responsible tremorgenic compounds in plants.
Impacts
(N/A)
Publications
- Goulart, C., Welch, K.D., Pfister, J.A., Goulart, D., Damasceno, A.D., Lee, S.T. 2018. Neurobehavioral evaluation of mice dosed with water hemlock green seeds and tubers. Poisonous Plant Research. 1(1):1-19.
- Pfister, J.A., Green, B.T., Gardner, D.R., Welch, K.D., Cook, D., Stonecipher, C.A. 2018. Grazing of Delphinium occidentale (duncecap larkspur) by susceptible and resistant cattle. Professional Animal Scientist. 34(6):581-593.
- Welch, K.D., Pfister, J.A., Cook, D., Carriao Dos Santos, F., Lee, S.T. 2018. Assessment of endophyte-derived tremorgenic compounds in Ipomoea asarifolia using mouse models. Toxicon. 156:52-60.
- Cunha, A., Medeiros, J., Riet-Correa, F., Gardner, D.R., Chaves, H., Silva Filho, G., Souza, F., Evencio Neto, J., Mendonca, F. 2018. Ipomoea brasiiana poisoning on buck reproduction. Ciencia Rural. 48(10):e20180061.
- Martinez, A., Lauroua, C., Borrelli, L.B., Gardner, D.R., Robles, C.S. 2018. Spontaneous outbreak of Astragalus pehuenches (Fabaceae) poisoning in cattle in Argentina. Toxicon. 157:84-86.
- Mendonca, F.S., Siva Filho, G.B., Chaves, H.A., Aires, L.D., Braga, T.C., Gardner, D.R., Cook, D., Buril, M.T. 2018. Detection of swainsonine and calystegines in Convolvulaceae species from the semiarid region of Pernambuco. Pesquisa Veterinaria Brasileira. 38(11):2044-2051.
- Stonecipher, C.A., Lee, S.T., Green, B.T., Cook, D., Welch, K.D., Pfister, J.A., Gardner, D.R. 2019. Evaluation of noninvasive specimens to diagnose livestock exposure to toxic larkspur (Delphinium spp.). Toxicon. 161:33-39.
- Lima, S.C., Godoy, K.C., Leal, P.V., Lee, S.T., Pfister, J.A., Souza, A.I., De Barros, C.S., Lemos, R.A. 2018. Toxicity of the different vegetative stages of Amorimia pubiflora to sheep. Toxicon. 158:47-50.
- Lee, S.T., Stonecipher, C.A., Carriao Dos Santos, F., Pfister, J.A., Welch, K.D., Cook, D., Green, B.T., Gardner, D.R., Panter, K.E. 2018. An evaluation of hair, oral fluid, earwax, and nasal mucus as noninvasive specimens to determine livestock exposure to teratogenic lupine species. Journal of Agricultural and Food Chemistry. 67(1):43⿿49.
- Roberts, G.K., Gardner, D.R., Foster, P.M., Howard, P.C., Lui, E., Walker, L., Van Breemen, R.B., Auerbach, S.S., Rider, C. 2018. Finding the bad actor: Challenges in identifying toxic constituents in botanical dietary supplements. Food and Chemical Toxicology. 124:431⿿438.
- Sillman, S.J., Lee, S.T., Claborn, J., Boruch, J., Harris, S.P. 2018. Fall panicum (Panicum dichotomiflorum) toxicosis in three juvenile goats. Journal of Veterinary Diagnostic Investigation. 31(1):90-93.
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Progress 10/01/17 to 09/30/18
Outputs
Progress Report Objectives (from AD-416): 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 (from AD-416): 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 Unit (PPRU) 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. 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. This is a bridging project which began January 2018, and continues research from 2080-32630-012-00D, "Understanding and Mitigating the Adverse Effects of Poisonous Plants on Livestock Production Systems", as the previous project reached its five-year maximum term. A new project for the next five years is undergoing Office of Scientific Quality Review. Please see the report for the previous project for additional information. Objective 1 and 2: Different herbicides to aid in the establishment of newly seeded grass species in revegetated rangelands infested with annual grasses that also contain populations of poisonous plants such as Lupines are being evaluated. How different toxins change in various toxic plants as a function of plant phenology is being investigated. Diverse species of several different genera (Delphinium, Astragalus) are being screened for their associated toxic principles to assess toxic risk. Objective 3, 4, and 5: Different non-invasive specimens to aid in diagnostic investigations are being evaluated. The responses of cattle to several different species of larkspur representing unique alkaloid profiles are under investigation. Animal specific factors such as age and how these factors influence an animal�s relative susceptibility to toxic plants such as larkspur are being assessed. Research to identify genetic markers that may explain differences in animal susceptibility due to poisonous plants such as larkspur is continuing. Accomplishments 01 Identification of tremorgenic (tremor causing) compounds. Various forage species including morning glories and grasses have been associated with a tremorgenic syndrome in livestock. ARS scientists in Logan, Utah, characterized the tremorgenic indole diterpenes in the forage plants, Ipomoea asarifolia, I. muelleri, and Elymus dahuricus, by high performance liquid chromatography � mass spectrometry (HPLC-MS) and nuclear magnetic resonance (NMR) spectroscopy. In addition, the chemical structure of three new compounds was determined and the toxicity of the suspected compounds was verified using a mouse model. This is the first detailed mass spectrometry analysis of indole diterpenes in these forages. These results will aid rangeland and livestock managers to better understand the potential problems associated with animals grazing rangelands and pasture infested with these plants. 02 Is tremetone the toxic compound in white snakeroot? White snakeroot can produce a disease called 'trembles" or "milk sickness" due to the putative toxin, tremetone, it contains. However, the toxicity of tremetone has not been demonstrated in vivo, or in a living organism. ARS scientists in Logan, Utah, demonstrated that dried white snakeroot stored for 5 years remains as toxic as it was soon after collection even though over 80 percent of the tremetone had disappeared, thus supporting other recent research indicating that tremetone concentration is not the singular indicator of plant toxicity. This information is important to livestock owners where white snakeroot can contaminate prepared feeds and be potentially toxic when ingested. 03 Transmammary transfer of toxicity to nursing kids. Rayless goldenrod (RGR), or Isodoma pluriform, poisons livestock in the southwestern U.S. by a toxin thought to be benzofuran ketones (i.e., tremetone). Goats have been used successfully as a model of RGR poisoning; however, the transmammary transfer of toxicity to offspring from lactating goats has not been studied. ARS scientists in Logan, Utah, conducted a study to determine if nursing kids would become poisoned via mother�s milk when the dams were dosed with RGR. Benzofuran ketones were not detected in the milk of lactating goats, nor did dosing with RGR alter milk composition. Kids became mildly poisoned from suckling dams dosed with RGR, but the concentration of the putative toxin was low in plant material, and undetectable in milk. Even so, the toxin is at least partially excreted in milk as kids eventually showed alterations in serum chemistry with milk as their only source of toxicity. These results demonstrate that milk products from RGR-poisoned animals should be avoided. 04 Genetic relationships among different chemotypes of Lupinus sulphureus. Lupines (Lupinus spp.) are a common plant legume species found on western U.S. rangelands. Lupinus spp. may contain quinolizidine and/or piperidine alkaloids that can be toxic and/or teratogenic to grazing livestock. The relative chemical profiles of these alkaloids may vary between and within a species. ARS scientists in Logan, Utah, investigated the characteristic alkaloid profiles of Lupinus sulphureus using field collections and the phylogenetic relationship of the different populations and chemotypes of L. sulphureus. The results showed that different chemotypes are represented by genetically distinct groups which in some cases may represent new species. This information helps us understand the diversity of lupine chemotypes and further supports the need for chemical analysis to assess the toxic potential of various lupine species. 05 A survey of swainsonine content in South American Astragalus species. Swainsonine is found in several plant species worldwide and causes severe toxicosis in livestock grazing these plants, especially Astragalus forages found throughout the temperate regions of the world. Some South American Astragalus species are reported to be toxic to livestock due to the toxin swainsonine but a systematic screen using modern chemical instrumentation is lacking. ARS scientists in Logan, Utah, and a South American collaborator using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry, detected swainsonine in 16 of 30 species screened using modern instrumentation, 14 of which had not been determined to contain swainsonine previously. Herbarium specimens were collected to assist in identification. This data set is a valuable tool for risk assessment and diagnostic purposes and highlights the utility of herbarium specimens in phytochemical studies.
Impacts
(N/A)
Publications
- Garcia, J.A., Garcia Y Santos, C., Rosas, J., Dutra, F., Gardner, D.R. 2018. A survey of Senecio spp. affecting livestock in Uruguay and their associated pyrrolizidine alkaloid content. Ciencia Rural. 48(2):1-7.
- Panter, K.E., Welch, K.D., Gardner, D.R., Lee, S.T., Green, B.T., Pfister, J.A., Cook, D., Davis, T.Z., Stegelmeier, B.L. 2018. Poisonous plants of the United States. In: Gupta, R.C., editor. Veterinary Toxicology, Basic and Clinical Principles. 3rd edition. Oxford, UK: Elsevier. p. 825-872.
- Pfister, J.A., Stegelmeier, B.L., Lee, S.T., Davis, T.Z., Green, B.T. 2018. Transmammary transfer of toxicity to nursing kids from Isocoma pluriflora (rayless goldenrod) dosed to lactating goats. Toxicon. 146:61-68.
- Colegate, S.M., Upton, R., Gardner, D.R., Panter, K.E., Betz, J.M. 2018. Potentially toxic pyrrolizidine alkaloids in Eupatorium perfoliatum and three related species. Implications for herbal use as boneset. Phytochemical Analysis. 29(6):613-626.
- Stegelmeier, B.L. 2018. The pathology of select poisonous plant-induced diseases in cattle. In: Buergelt, C.D., Clark, E.G., Del Piero, F., editors. Bovine Pathology: Text and Color Atlas. Boston, MA: CABI. p. 381- 417.
- Stegelmeier, B.L., Davis, T.Z. 2018. Toxic causes of intestinal disease in horses. Veterinary Clinics of North America. 34(1):127-139.
- Shi, C., An, S., Yao, Z., Young, C.A., Panaccione, D.G., Lee, S.T., Schardl, C.L., Li, C. 2018. Toxin-producing Epichlo� bromicola strains symbiotic with the forage grass Elymus dahuricus in China. Mycologia. 109(6):847-859.
- Davis, T.Z., Stegelmeier, B.L., Lee, S.T., Green, B.T., Chitko-Mckown, C.G. 2018. Effects of grinding and long-term storage on the toxicity of white snakeroot (Ageratina altissima) in goats. Research in Veterinary Science. 118:419-422.
- Green, B.T., Gardner, D.R., Cook, D., Pfister, J.A., Welch, K.D., Keele, J. W. 2018. Age-dependent intoxication by larkspur (Delphinium) in Angus steers. Toxicon. 152:57-59.
- Cook, D., Gardner, D.R., Martinez, A., Robles, C., Pfister, J.A. 2018. A screen for swainsonine among South American Astragalus species. Toxicon. 139:54-57.
- Cook, D., Mott, I.W., Larson, S.R., Lee, S.T., Johnson, R., Stonecipher, C. A. 2018. Genetic relationships among different chemotypes of Lupinus sulphureus. Journal of Agricultural and Food Chemistry. 66(8):1773-1783.
- Welch, K.D., Lee, S.T., Cook, D., Gardner, D.R., Pfister, J.A. 2018. Chemical analysis of plants that poison livestock: Successes, challenges, and opportunities. Journal of Agricultural and Food Chemistry. 66(13):3308- 3314.
- Gardner, D.R., Welch, K.D., Lee, S.T., Cook, D., Riet-Correa, F. 2018. Tremorgenic indole diterpenes from Ipomoea asarifolia and Ipomoea muelleri and the identification of 6,7-dehydro-11-hydroxy-12,13-epoxyterpendole A. Journal of Natural Products. 81(7):1682-1686.
- Harrison, J.G., Parchman, T.L., Cook, D., Gardner, D.R., Forister, M.L. 2018. A heritable symbiont and host-associated factors shape fungal endophyte communities across spatial scales. Journal of Ecology. 1-13.
- Fitch, R.W., Snider, B.B., Zhou, Q., Foxman, B.M., Pandya, A.A., Yakel, J. L., Olson, T., Al-Muhtasib, N., Xiao, Y., Welch, K.D., Panter, K.E. 2018. Absolute configuration and pharmacology of the poison frog alkaloid phantasmidine. Journal of Natural Products. 81(4):1029-1035.
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