Foothill death camas [Zigadenus paniculatus; or Toxicoscordion paniculatum] is one of about 15 death camas species in North America that is poisonous to grazing livestock. The major toxins in death camas are zygadenine and zygacine, the 3-acetyl ester of zygadenine. However, during plant flower to seed pod growth stages, 3-angeloylzygadenine and 3-veratroylzygadenine become major alkaloids in these reproductive tissues. We hypothesized that 3-angeloylzygadenine, and 3-veratroylzygadenine would be metabolized by esterases in liver, plasma, and rumen to zygadenine. Three death camas alkaloids, zygacine (as a positive control), 3-angeloylzygadenine, and 3-veratroylzygadenine were evaluated with in vitro rumen, plasma and liver S9 incubations. Results from these experiments indicated that 3-veratroylzygadenine was metabolized but not 3-angeloylzygadenine. To confirm the in vitro metabolism results, sheep were orally dosed death camas plant material containing only the reproductive parts of the plants, blood was collected by venipuncture, and alkaloid concentrations measured. The metabolism of 3-veratroylzygadenine but not 3-angeloylzygadenine was confirmed with the in vivo sheep dosing experiments, and we accepted our esterase metabolism hypothesis for 3-veratroylzygadenine.

Larkspurs (Delphinium spp.) are one of the most problematic plants for cattle producers in North America. Previous research has shown that there is a difference in the alkaloid composition between different species of larkspurs, and between different populations of the same species. Differences in the chemical profiles of the various larkspurs and their associated toxicities in rodent models and in cattle have been documented. However, different methods were used to analyze the plant material and to characterize its toxicity. In this study, plant material from 20 larkspur collections was extracted using the same method and analyzed using the same liquid chromatography-mass spectrometry method, and the acute toxicity of each extract was tested using a mouse median lethal dose assay with the same strain of mice purchased from one vendor. The results from this study demonstrate the large variations in alkaloid composition and concentrations between the various species and populations of larkspurs in the western USA. The data also demonstrate a strong correlation between the N-(methylsuccinimido) anthranoyllycoctonine alkaloid content of the plant and its toxicity in a mouse model. The results from this study provide a standardized comparison of the risk of some of the more common and problematic larkspurs in the western USA.

Over a 2-wk period, 20 cows that were grazing a Megathyrsus maximus (Guinea grass) pasture died after developing depression, respiratory difficulty, and recumbency. Affected animals had increased serum urea, phosphorus, and creatinine concentrations, and below-normal calcium concentrations. Autopsy revealed moderate ascites; mildly enlarged, pale, mottled kidneys; and perirenal edema. Microscopically, there was hyperplasia of mesangial cells in the renal glomeruli, renal tubular epithelial necrosis, and hyaline casts and refractive crystals in cortical and medullary renal tubular lumens. Samples of M. maximus from the affected pasture contained elevated concentrations of soluble oxalate (3.71%). Our findings suggest that oxalate produced by M. maximus caused acute tubular injury. Our case highlights the critical need for monitoring oxalate levels in pastures and managing grazing practices, particularly under drought conditions, to prevent similar outbreaks in the future.

Cannabis sativa (varieties for industrial use or animal feed are termed hemp), and its extracted byproducts are being considered for animal feed due to their high protein content. However, if hemp disrupts fertility and reproduction in livestock, it should not be used as a feed source. We hypothesized that the phytocannabinoids in hemp would disrupt fertility and reproduction, cause craniofacial defects (cyclops, cleft palate, misshapen head), and low birth weight in lambs. To test this hypothesis, 22 timed pregnant ewes were dosed with hemp in the form of dried ground hemp plant material at 150 mg/kg body weight per day total cannabinoids, and from gestational days 10 to 20 and a separate 22 timed pregnant ewes were dosed similarly with dried ground grass hay as a control. The most prevalent cannabinoids in the plant material were cannabidiolic acid (CBDA) at a concentration of 23.2 mg/g, and cannabidiol (CBD) at a concentration of 5.8 mg/g. Delta 9-tetrahydrocannabidiol was present in the plant material at a concentration of 0.3 mg/g. The hemp used in this study had crude protein concentrations of 15.6%, neutral detergent fiber concentrations of 42.2%, and in vitro true digestibility concentrations of 83.6%. After 10 d of dosing with hemp, a serum sample was obtained from each of the ewes, CBDA was measured at a concentration of 652 ± 38 ng/mL and CBD was measured at 16 ± 0.9 ng/mL. THC was not detected in the serum. The average gestation length for lambs from the hemp treated ewes was 148 ± 0.38 d, and the average gestation length for lambs from the grass hay treated ewes was 149 ± 0.38 d (P = 0.23). The numbers of male and female lambs did not significantly vary from expected (50:50) (P = 0.32). There were no significant fetal deformities (P > 0.05) or weight differences between the treatment groups (P > 0.05), and as expected, the lamb weights significantly increased over time (P < 0.05). These results suggest that Cannabis sativa may have the potential with further research to be a suitable protein source for gestating sheep.

Plants produce an array of defensive compounds with toxic or deterrent effects on insect herbivores. Pollen can contain relatively high concentrations of such defense compounds, but the causes and consequences of this enigmatic phenomenon remain mostly unknown. These compounds could potentially protect pollen against antagonists but could also reduce flower attractiveness to pollinators. We combined field observations of the pollen-rewarding Lupinus argenteus with chemical analysis and laboratory assays to test three hypotheses for the presence of pollen defense compounds: (1) these compounds are the result of spillover from adjacent tissues, (2) they protect against pollen thieves, and (3) they act as antimicrobial compounds. We also tested whether pollen defense compounds affect pollinator behavior. We found a positive relationship between alkaloid concentrations in pollen and petals, supporting the idea that pollen defense compounds partly originate from spillover. However, pollen and petals exhibited quantitatively (but not qualitatively) distinct alkaloid profiles, suggesting that plants can adjust pollen alkaloid composition independently from that of adjacent tissues. We found no relationship between pollen alkaloid concentration and the abundance of pollen thieves in Lupinus flowers. However, pollen alkaloids were negatively associated with bacterial abundance. Finally, plants with more alkaloids in their pollen received more pollinator visits, but these visits were shorter, resulting in no change in the overall number of flowers visited. We propose that pollen defense compounds are partly the result of spillover from other tissues, while they also play an antimicrobial role. The absence of negative effects of these compounds on pollinator visitation likely allows their maintenance in pollen at relatively high concentrations. Taken together, our results suggest that pollen alkaloids affect and are mediated by the interplay of multiple interactions.

Evidence-based therapies to manage the clinical signs of intoxication caused by toxic plants in livestock are lacking. For that reason, the aim of this work was to develop a drug-based intervention for the management of clinical signs of piperidine alkaloid intoxication in livestock. The actions of anabasine, coniine, gamma-coniceine, and two total alkaloid extracts from Lupinus sulphureus were compared in the presence and absence of the nicotinic acetylcholine receptor partial agonist varenicline in RD cells, mice and goats. Pretreatment of RD cells with 10.0 mu M varenicline significantly shifted the anabasine fifty percent effective concentration (EC50) value to a greater concentration and blocked the response of the cells to coniine. gamma-coniceine did not have any effect on RD cells as measured by membrane potential sensing dye. Swiss Webster mice median lethal dose (LD50) values for anabasine, coniine, gamma-coniceine were 1.5, 5.5, and 3.7 mg/kg respectively, and pretreatment with 10.0 mg/kg i. p. dosed varenicline shifted the LD50 values to 4.2, 9.1, and 4.3 mg/kg respectively. The rodent LD50 value of the Pendelton, WA L. sulphureus quinolizidine alkaloid extract was shifted to a lesser concentration by varenicline while the Ritzville, WA L. sulphureus piperidine alkaloid extract was shifted to a greater concentration by varenicline. The clinical signs of intoxication in goats orally dosed with Conium maculatum were exacerbated by 0.5, 1.0 and 10.0 mg/kg i. v. dosed varenicline. These results suggest that varenicline was effective at shifting piperidine alkaloid EC50 values in RD cells and increasing piperidine but not quinolizidine alkaloid LD50 values in mice and was not useful at managing the clinical signs of poison hemlock intoxication in goats.

Death Camas (Zigadenus spp.) are common poisonous plants distributed throughout North America. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. Both cattle and sheep can be poisoned by grazing death camas, however, sheep consume death camas more readily and are most often poisoned. We hypothesized that the presence of enzymes, including esterases present in the rumen, liver, and blood of livestock would metabolize zygacine. The objective of this study was to investigate the metabolism of zygacine in sheep and cattle using in-vitro and in-vivo systems. Results from experiments where zygacine was incubated in rumen culture, plasma, liver S9 fractions, and liver microsomes and from the analysis of rumen and sera from sheep and cattle dosed death camas plant material demonstrated that zygacine is metabolized to zygadenine in the rumen, liver and blood of sheep and cattle. The results from this study indicate that diagnosticians should analyze for zygadenine, and not zygacine, in the rumen and sera for the diagnosis of livestock suspected to have been poisoned by foothill death camas.

Foothill death camas (Zigadenus paniculatus) is a common poisonous plant found throughout western North America. The toxic alkaloids in foothill death camas are zygadenine, esters of zygadenine, with zygacine, the 3-acetyl ester of zygadenine, often being the most abundant. Two additional esters of zygadenine that are found primarily in the floral parts of foothill death camas are 3-angeloylzygadenine and 3-veratroylzygadeine. Recent research has shown that very little zygacine is detected in the blood of animals dosed with zygacine. A recent investigation into the metabolism of zygacine demonstrated that zygacine is rapidly metabolized to zygadenine, demonstrating a clear first pass effect. The objective of this study was to determine if there is a difference in the acute toxicity of zygacine and zygadenine to mice and sheep. Additionally, two other esters of zygadenine, 3-angeloylzygadenine and 3-veratroylzygadenine, were evaluated for their acute toxicity in a mouse IV LD50 assay. All three esters of zygadenine tested were more toxic than zygadenine, with the following rank order of toxicity in the mouse IV LD50 assay: zygadenine-HCl (59.5 mg/kg) < zygacine-HCl (1.6 mg/kg) < angeloylzygadenine-HCl (1.0 mg/kg) < veratroylzygadenine-HCl (0.5 mg/kg). Similar to the results of the mouse experiments, zygacine-HCl was significantly more toxic than zygadenine-HCl in sheep dosed IV with pure compounds. Sheep dosed with 1.25 mg/kg zygacine-HCl showed severe clinical signs of poisoning. Whereas a dose of 12.5 mg/kg zygadenine-HCl was required to elicit a similar onset and severity of clinical signs. Overall, these data indicate that zygacine is more toxic than zygadenine when administered IV, when first pass metabolism is bypassed.

The Mississippi State University College of Veterinary Medi­cine Ambulatory Service examined a 3-year-old Charolais-cross cow on October 19, 2023, for lateral recumbency, inabil­ity to rise and generalized tremors. Within 4 hours following initial case discovery, 20 additional cases were discovered in 2 adjacent pastures, including one mortality. Clinical signs ranged in severity from mild tremors to severe ataxia, hy­perexcitability, aggression, lateral recumbency and death. All affected cows had calved in the spring of 2023, and all 2023 spring calves were weaned 3 days prior on October 16. Overnight on October 16-17, one group of cows pushed down a fence, and 32 cows entered a pasture adjacent to their weaned calves. Following discovery of cases on October 19, all cattle were removed from the affected pasture and grass hay was provided immediately. Necropsy of 2 affected animals as well as serum chemistries of 5 affected cows revealed non-specific findings. However, abundant dallisgrass (Paspalum dilatatum) with obvious Claviceps paspali infection was present on the pasture that the cattle entered overnight on October 16-17. High-performance liquid chromatography-mass spectrom­etry (HPLC-MS) analysis of samples collected from C. paspali infected pasture as well as rumen and abomasum contents collected at necropsy revealed several tremorgenic indole di­terpene alkaloids. Additionally, DNA metabarcoding of rumen contents and forage samples confirmed the ingestion of dallis­grass infected with C. paspali. Upon recheck on October 20, all previously affected cows appeared to be recovering, and com­plete resolution of clinical signs had occurred by October 23.

Lupines are responsible for a condition in cattle referred to as "crooked calf syndrome" (CCS) that occurs when pregnant cattle graze teratogenic lupines. A proposed management strategy to limit these types of birth defects includes utilizing an intermittent grazing schedule to allow short durations of grazing lupine-infested areas interrupted by movement to a lupine-free pasture. The objective of this study was to determine if an intermittent schedule of ten continuous days of lupine treatment followed by 5 d off treatment would be sufficient to decrease, or prevent, the incidence of lupine-induced malformations. Continuous dosing of the teratogenic lupine (Lupinus leucophyllus) to pregnant cows for 30 d during the most susceptible stage of pregnancy (gestation days 40 to 70) resulted in severe skeletal birth defects in their calves. However, intermittent dosing of the teratogenic lupine demonstrated that interrupted intake of lupine reduced the severity, or eliminated, permanent skeletal malformations in calves born to cows dosed lupine. Toxicokinetic and ultrasound data demonstrated a clear inverse correlation between serum anagyrine (the primary teratogenic alkaloid in some lupines) concentrations in the dam and fetal movement. In the intermittent group, fetal movement quickly returned to normal after lupine feeding stopped and remained normal until lupine treatment resumed. Therefore, interrupting lupine intake for at least 5 d through an intermittent grazing program could reduce the severity of the CCS. Furthermore, this method would allow ranchers to move cattle back into lupine pastures after a brief interruption, which would allow for more efficient utilization of forage resources. An intermittent lupine dosing regimen in pregnant cattle of 10 d on, 5 d off, significantly prevents skeletal malformations from occurring. Therefore, a grazing rotation that results in intermittent exposure to teratogenic lupines can reduce the occurrence of crooked calf syndrome. Lupines are responsible for a condition in cattle referred to as "crooked calf syndrome" (CCS) that occurs when pregnant cattle graze teratogenic lupines. A proposed management strategy to limit these types of birth defects includes utilizing an intermittent grazing schedule to allow short durations of grazing lupine-infested areas interrupted by movement to a lupine-free pasture. The objective of this study was to determine if an intermittent schedule of ten continuous days on lupine treatment followed by 5 d off treatment would be sufficient to decrease, or prevent, the incidence of lupine-induced malformations. The data reported in this study demonstrate that interrupting lupine intake for at least 5 d through an intermittent grazing program could reduce the severity of the CCS. Furthermore, this method would allow ranchers to move cattle back into lupine pastures after a brief interruption, which would allow for more efficient utilization of forage resources.

Lupines (Lupinus spp.) are a common plant species on western U.S. rangelands with several lupine species containing alkaloids that can be toxic and/or teratogenic to livestock. In North America, more than 150 lupine species are recognized with some ranches or grazing allotments containing multiple species. One or more of these lupine species may contain alkaloids that are teratogenic to cattle. Previous work has shown that lupine alkaloids can be detected in earwax of cattle grazing lupine infested rangelands. Our hypothesis is that earwax can be used to determine if cattle have been exposed to teratogenic alkaloids from multiple lupine species. Two lupine species, L. sericeus and L. polyphyllus, were present on a rangeland in east-central Idaho. The teratogen, anagyrine, was detected in L. sericeus and the teratogen, ammodendrine, was detected in L. polyphyllus plants collected on this rangeland. In this study, earwax was collected from 69 pregnant cows that had previously grazed a rangeland containing two different lupine species containing alkaloids that cause crooked calf syndrome (CCS). Anagyrine was detected in the earwax of all 69 cows sampled. Ammodendrine, was detected in the earwax of 28 of the 69 cows sampled. Earwax is a good non-invasive sample to aid in the diagnosis of cattle that have consumed lupine and does appear, in this case, to be a good diagnostic tool to differentiate between more than one lupine species that may be the cause of CCS. Concentrations of anagyrine or ammodendrine did not correlate with the incidence of CCS.

Foothill death camas (Z. paniculatus) grows on the foothill ranges of western North America and is acutely toxic to livestock grazing these ranges. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. In this study, earwax was evaluated as a specimen to determine livestock exposure to foothill death camas. Death camas alkaloids were detected in the earwax of sheep administered oral doses of foothill death camas alkaloids. In addition, death camas alkaloids were detected in the earwax of sheep that grazed rangeland with abundant death camas. This study demonstrates the potential of earwax as a noninvasive specimen for chemical analyses to aid in the diagnosis of livestock that may have been exposed to and poisoned by death camas. The results from this study indicate that diagnosticians should analyze for zygacine and zygadenine in the earwax of livestock suspected to have been poisoned by foothill death camas.

Taxus is a genus of coniferous shrubs and trees, commonly known as the yews, in the family Taxaceae. All species of yew contain taxine alkaloids, which are ascribed as the toxic principles. Anecdotally, free ranging ruminants such as antelope, deer, elk, and moose have been regarded as tolerant to yew. Herein several cases of intoxication of deer, elk, and moose by yew from the state of Utah in the winter of 2022-2023 are documented. Ingestion of yew was documented by three means among the poisoned cervids; plant fragments consistent with yew were visually observed in the rumen contents, chemical analysis, and subsequent detection of the taxines from rumen and liver contents, and identification of exact sequence variants identified as Taxus species from DNA metabarcoding. Undoubtedly, the record snowfall in Utah during the winter of 2022-2023 contributed to these poisonings.

Due to climate change and increasing summer temperatures, tropical cattle may graze where temperate cattle have grazed, exposing tropical cattle to toxic plants they may be unfamiliar with. This work compared the toxicity of Lupinus leucophyllus (velvet lupine) in temperate and tropical cattle. Orally dosed velvet lupine in tropical cattle caused death. If producers opt to graze tropical cattle, additional care must be taken on rangelands where toxic lupines like velvet lupine grow.

Heritable fungal endosymbiosis is underinvestigated in plant biology and documented in only three plant families (Convolvulaceae, Fabaceae, and Poaceae). An estimated 40% of morning glory species in the tribe Ipomoeeae (Convolvulaceae) have associations with one of two distinct heritable, endosymbiotic fungi (Periglandula and Chaetothyriales) that produce the bioactive metabolites ergot alkaloids, indole diterpene alkaloids, and swainsonine, which have been of interest for their toxic effects on animals and potential medical applications. Here, we report the occurrence of ergot alkaloids, indole diterpene alkaloids, and swainsonine in the Convolvulaceae; and the fungi that produce them based on synthesis of previous studies and new indole diterpene alkaloid data from 27 additional species in a phylogenetic, geographic, and life-history context. We find that individual morning glory species host no more than one metabolite-producing fungal endosymbiont (with one possible exception), possibly due to costs to the host and overlapping functions of the alkaloids. The symbiotic morning glory lineages occur in distinct phylogenetic clades, and host species have significantly larger seed size than nonsymbiotic species. The distinct and widely distributed endosymbiotic relationships in the morning glory family and their alkaloids provide an accessible study system for understanding heritable plant-fungal symbiosis evolution and their potential functions for host plants.

The United States National Cancer Institute defines a biomarker as: "A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease." In Veterinary Medicine, biomarkers associated with plant poisonings of livestock have great utility. Since grazing livestock poisoned by toxic plants are often found dead, biomarkers of plant poisoning allow for a more rapid postmortem diagnosis and response to prevent further deaths. The presence and concentration of toxins in poisonous plants are biomarkers of risk for livestock poisoning that can be measured by the chemical analysis of plant material. More difficult is, the detection of plant toxins or biomarkers in biological samples from intoxicated or deceased animals. The purpose of this article is to review potential biomarkers of plant poisoning in grazing livestock in the Western North America including recently investigated non-invasive sampling techniques. Plants discussed include larkspur, lupine, water hemlock, swainsonine-containing plants, selenium-containing plants, and pyrrolizidine alkaloid containing plants. Other factors such as animal age and sex that affect plant biomarker concentrations in vivo are also discussed.

Core IdeasSwitchgrass has various ecosystem benefits.Switchgrass cultivars Liberty and Independence were evaluated for steroidal saponins.Steroidal saponins were detected in all leaf and stem tissues of both Liberty and Independence cultivars.Steroidal saponins may reduce aboveground pests and influence soil nutrient and water dynamics.

Nitrogen-fixing legumes such as alfalfa (Medicago sativa L.) and sainfoin (Onobrychis viciifolia Scop.) may benefit agricultural systems. In addition to quality forage, both legumes contain secondary metabolites that play important roles in agroecological systems. Alfalfa contains triterpenes (saponins), and sainfoin contains phenolic compounds (tannins). Terpenes and phenolics can influence soil nutrient dynamics by inhibiting microbial activity, which could slow nitrogen mineralization and minimize nitrogen losses. However, research evaluating their influence in the soil has largely come from silviculture or laboratory studies. Therefore, we initiated a field study in Lewiston, UT, assessing how alfalfa and sainfoin influence soil characteristics. The randomized split-plot block design had three replicates and included a fertilized bale-and-remove system, a green manure system (leaving mown plant forage in the field), and a no-fertilizer bale-and-remove system. We measured saponin and condensed tannin (CT) concentrations in alfalfa and sainfoin, respectively, forage biomass, and soil characteristics [e.g., ammonium (NH4), nitrate (NO3), dehydrogenase, organic C, soil respiration, etc.]. Green manure plots showed greater microbial respiration (p = .02), microbial biomass (p < .01), and readily mineralized carbon (p = .04) than other systems. Forage biomass was greater in sainfoin than in alfalfa (p < .001), whereas soil NO3 was greater in alfalfa than in sainfoin (p < .01). The soil NO3 differences could be explained by the inhibition of mineralization by CT in sainfoin compared with the saponins in alfalfa. Planting forages containing tannins may reduce nitrogen losses, thereby enhancing agricultural sustainability.

Brachiaria species are some of the most used forage species for raising Brazilian cattle because of their great nutritional value and adaptability to the tropical climate. However, cases of animal intoxication have been described. Animal species, age, genetic resistance, and previous adaptation to the forage can influence the susceptibility to intoxication. Cattle (young or adults), other adult ruminants and animals adapted to consumption (experienced flocks) are considered more resistant. The main clinical presentation is that of hepatogenous photosensitization. Brachiaria brizantha and Brachiaria ruziziensis are considered less toxic. The aim of this study is to describe three outbreaks of intoxication by B. brizantha and B. ruziziensis in experienced cattle, as well as to compare the concentrations of protodioscin in paddocks with and without clinical cases. It was observed that the two forage species are toxic to all age groups of cattle adapted to their consumption, and the concentrations of protodioscin present in the plant cannot be used as the only criterion for determining the occurrence of intoxication.