Neurobehavioral evaluation of mice dosed with water hemlock green seeds and tubers

Authors: GOULART, CAMILA - Federal University Of Goias; Welch, Kevin; Pfister, James; GOULART, DANIEL - Federal University Of Goias; DAMASCENO, ADILSON - Federal University Of Goias; Lee, Stephen

Submitted to: International Journal of Poisonous Plant Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2018
Publication Date: 10/1/2018
Citation: 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. https://doi.org/10.26077/sk8v-xz71.
DOI: https://doi.org/10.26077/sk8v-xz71

Interpretive Summary: Cicuta douglasii, C. maculata, C. virosa and C. bulbifera (Apiaceae family) are perennial forbs generally known as water hemlock. All Cicuta spp. are highly toxic to livestock and humans. The water hemlocks are considered economically important to livestock because the plants are often found in pastures of North America and Europe and the poisoning of cattle leads most often to death. Most field cases of poisoning by Cicuta spp. occur after intake of the tuber. However, studies also suggest that the green seeds are also toxic. The relative toxicity of other plant parts and the influence of plant age on toxicity warrant investigation. Moreover, there is no information about how the toxin might interfere with motor activity, or other aspects of behavior in poisoned animals. The objectives of this study were to determine the toxicity of different parts of water hemlock, and to investigate behavioral disorders and motor incoordination in poisoned animals using a mouse model. The results from this study demonstrated that among the parts of water hemlock studied, only the green seeds and the tubers were toxic when dosed orally in mice, and tubers were more toxic than green seeds. Tuber extracts were especially potent in causing a decrease in motor activity and depression, while periodically provoking seizures. However, no changes in muscle strength were observed. Further research will be required to identify, quantitate, and purify cicutoxin and the other polyacetylene compounds from the various water hemlock plant parts for future studies on toxicity and effects on motor function.

Technical Abstract: Water hemlock are plants of the genus Cicuta and are toxic to animals and humans. The primary toxin is cicutoxin, which is abundant in the tubers, but less abundant in other parts of the plant. Other cicutoxin-like compounds, such as cicutols, may also contribute to the toxicity of water hemlock, are more abundant in non-tuber plant parts. The objective of this study was to determine the toxicity of different parts of water hemlock and characterize their effects on motor function/coordination in mice. An aqueous extract of green seeds, dry seeds, tubers, flowers and stems of water hemlock was dosed orally to mice to determine the LD50. The results indicated that only the green seeds and tubers were sufficiently toxic to animals to induce clonic-tonic seizures and death. The LD50 for tubers and green seeds was 17 mg/kg and 1320 mg/kg, respectively. Several tests were used to evaluate motor function and behavior in treated mice including grip strength, rotarod, tremor monitor, and open field. The animals were evaluated before dosing and 30, 90, 120, 150, 180, 240, and 300 min after dosing. In summary, water hemlock affected muscle function of mice, including their ability to grasp and hold onto objects, their balance and motility on a rotarod, motor activity, and exploratory and anxiety-related (i.e., thigmotaxis) behaviors in an open field. Seizures interspersed with CNS depression were observed in animals poisoned by water hemlock.