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Title: An evaluation of the toxicity of white snakeroot (Ageratina altissima) and rayless goldenrod (Isocoma pluriflora) in a lactating mouse model

Author
item Welch, Kevin
item Lee, Stephen
item Davis, Thomas - Zane

Submitted to: International Journal of Poisonous Plant Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/11/2015
Publication Date: 10/24/2017
Citation: 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/

Interpretive Summary: Both rayless goldenrod (RGR) and white snakeroot (WSR) have been known to be poisonous to livestock and humans for many years. They both cause very similar clinical signs of poisoning, including muscle weakness and tremors. Additionally, they both contain similar benzofuran ketones (BFK). Even though it has been suggested that the BFK are the toxic components of these plants, this has not been demonstrated in a mammalian model. To this end a number of small animal models have been previously evaluated, including several rodent species. All research to date suggests that adult rodents, with guinea pigs possibly an exception, are not a good model to study the toxicity of these plants. It is however, quite common for neonatal animals to be more sensitive to toxins that mature, adult animals. Therefore the objective of this study was to determine if a lactating mouse model can be used to study the toxicity of RGR and WSR, with the end goal of identifying the toxic component(s) of RGR and WSR. The data from this study suggest that neither WSR nor RGR are toxic to lactating mice, nor their pups. Consequently, mice do not appear to be a viable small animal model to study the toxicity of RGR or WSR. Future work will continue to try and identify a suitable small animal model that can be used to identify and characterize the toxic compounds in WSR and RGR.

Technical Abstract: Rayless goldenrod (Isocoma pluriflora) and white snakeroot (Ageratina altissima) have been implicated in the poisoning of various livestock species including cattle, sheep, goats, and horses as well as humans. It has also been observed that nursing young can be poisoned when their mothers consume these plants, indicating that the toxins are excreted in the milk. Both plants contain similar benezofuran ketones, which have been suggested to be the toxins. However, recent research suggests that another compound(s) may be responsible. Consequently, additional research needs to be done to definitively identify and characterize the toxic component(s) of these plants. The objective of this study was to determine if a lactating mouse model can serve as a good small animal model to study the toxicity of white snakeroot and rayless goldenrod, with the end goal of identifying the toxin(s) in these plants. White snakeroot and rayless goldenrod were dosed orally, via the chow, to lactating dams from post natal days (PND) 1-21. The pups were evaluated for locomotor activity as well as motor coordination and function on PND 14, 21, and 28. There was no indication of muscle weakness or tremors in any of the dams or their pups. The results from this study suggest that neither white snakeroot nor rayless goldenrod are toxic to lactating mice nor their pups. Consequently, mice do not appear to be a viable small animal model to study the toxicity of these plants. Future work is needed to identify a suitable small animal model that can be used to aid in the identification and characterization of the toxic compounds in white snakeroot and rayless goldenrod.