Identification of two death camas chemotypes within a population and evaluation of toxicity.

Foothill death camas (Zigadenus paniculatus) is a native, cool-season, bulbous perennial forb found throughout the western U.S. The toxins in death camas are steroidal alkaloids. Zygacine is often the most abundant alkaloid in death camas and is believed to be the primary toxic component. A population of death camas with plants consisting of two different chemical profiles (chemotypes) growing within the same location were identified. The objective of this study was to determine the percentage of a death camas population represented by each of the different chemotypes and to determine if there was a difference in toxicity between the two chemotypes. One third of the population sampled consisted of chemotype 1, while two-thirds of the population consisted of chemotype 2. The zygacine concentration of chemotype 1 was three times higher than chemotype 2. Chemotype 2 contained higher concentrations of several other steroidal alkaloids than chemotype 1. We hypothesized that chemotype 1, which consisted of higher concentrations of zygacine, would be more toxic than chemotype 2. The acute toxicity of each chemotype was determined in mice and sheep. In the mouse LD50 study, the acute toxicity of the chemotype 1 alkaloids (2.3 mg/kg BW) was different than the chemotype 2 alkaloids (3.2 mg/kg BW). However, in the sheep study there were no differences in the adverse effects between chemotypes. Based upon the results of this study, caution should be taken when livestock are grazing death camas, as both chemotypes of death camas appear to pose a similar risk to grazing livestock.

Analysis of rumen contents and ocular fluid for toxic alkaloids from goats and cows dosed larkspur (Delphinium barbeyi), lupine (Lupinus leucophyllus), and death camas (Zigadenus paniculatus).

Larkspurs, lupines, and death camas can be acutely toxic to livestock and are serious poisonous plant problems in western North America. The toxicity of these plants depends on the composition and concentrations of the toxic alkaloids in the plants. In this study, goats and cows were dosed sub-lethal doses of larkspur, lupine, and death camas. Rumen contents and ocular fluid samples were collected, and simple extraction, sample preparation, and analytical methods were developed for the detection of toxic alkaloids in the rumen contents and ocular fluid samples. Toxic alkaloids were detected in the rumen contents and ocular fluid samples from the goats and cows dosed larkspur, lupine, and death camas. In addition, results from a case report where rumen contents were analyzed from a steer that was suspected to have died due to larkspur are reported. This demonstrates the utility of the methods described for the diagnosis of acute plant poisonings.

The Effect of Co-Administration of Death Camas (Zigadenus spp.) and Low Larkspur (Delphinium spp.) in Cattle.

In many rangeland settings, there is more than one potential poisonous plant. Two poisonous plants that are often found growing simultaneously in the same location in North American rangelands are death camas (Zigadenus spp.) and low larkspur (Delphinium spp.). The objective of this study was to determine if co-administration of death camas would exacerbate the toxicity of low larkspur in cattle. Cattle dosed with 2.0 g of death camas/kg BW showed slight frothing and lethargy, whereas cattle dosed with both death camas and low larkspur showed increased clinical signs of poisoning. Although qualitative differences in clinical signs of intoxication in cattle co-treated with death camas and low larkspur were observed, there were not any significant quantitative differences in heart rate or exercise-induced muscle fatigue. Co-treatment with death camas and low larkspur did not affect the serum zygacine kinetics, however, there was a difference in the larkspur alkaloid kinetics in the co-exposure group. Overall, the results from this study suggest that co-exposure to death camas and low larkspur is not significantly more toxic to cattle than exposure to the plants individually. The results from this study increase our knowledge and understanding regarding the acute toxicity of death camas and low larkspur in cattle.

The effect of low larkspur (Delphinium spp.) co-administration on the acute toxicity of death camas (Zigadenus spp.) in sheep.

In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in the same area. Two poisonous plants that are often found growing simultaneously in the same location are death camas (Zigadenus spp.) and low larkspur (Delphinium spp.). Sheep are known to be susceptible to death camas poisoning while they are thought to be resistant to larkspur. The objective of this study was to determine if co-administration of low larkspur would exacerbate the toxicity of death camas in sheep. A dose finding study was performed to find a dose of death camas that caused minimal clinical signs of poisoning. Sheep were observed for clinical signs of poisoning as well as changes in heart rate and muscle fatigue. Sheep dosed with 1.14 g of death camas per kg BW showed slight frothing and lethargy, whereas sheep dosed with death camas and low larkspur showed slightly more noticeable clinical signs of poisoning. Sheep dosed with only low larkspur, at 7.8 g/kg BW, showed no signs of poisoning. Although we observed a qualitative difference in clinical signs of intoxication in sheep co-treated with death camas and low larkspur we did not detect any quantitative differences in heart rate, exercise-induced muscle fatigue, or differences in serum zygacine kinetics. Consequently, the results from this study suggest that low larkspur does not affect the toxicity of death camas in sheep. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas and low larkspur in sheep. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for ranchers and in designing additional experiments to study the toxicity of death camas to other livestock species.

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

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

Zigadenus poisoning treated with atropine and dopamine.

INTRODUCTION: Zigadenus (commonly known as "death camas" or "mountain camas") is a common plant in the lily family found throughout the United States. Its onion-like roots can be mistaken for an edible plant. Ingestion may cause hemodynamic instability which has successfully been treated with atropine. It has been suggested that vasopressors may be an effective therapy for this ingestion. We report the successful use of dopamine as therapy in Zigadenus ingestion. CASE REPORT: A 45 year-old, previously healthy male presented to the ED with complaints of severe nausea and vomiting after ingesting two "wild onion" bulbs. He was noted to have marked hypotension and bradycardia in the ED, which initially responded to treatment with IV fluids and atropine. The plant was identified as a species of Zigadenus. After a second drop in heart rate and blood pressure in the ICU, hypotension and bradycardia were treated successfully with a dopamine infusion. DISCUSSION: Zigadenus ingestion presents with vomiting, hypotension and bradycardia. The hemodynamic instability responded well to atropine for 1-2 hours. Dopamine infusion was used to stabilize both heart rate and blood pressure. With supportive care, poisoned individuals become relatively asymptomatic within 24 hours of their ingestion. Patients may be discharged once asymptomatic, typically the day after ingestion, and do not have any known long term sequelae. CONCLUSION: Zigadenus poisoning causes vomiting, hypotension and bradycardia. The hemodynamic instability may be treated with atropine administration and dopamine infusion.