Microsomal activation, and SH-SY5Y cell toxicity studies of tremetone and 6-hydroxytremetone isolated from rayless goldenrod Isocoma pluriflora and white snakeroot Agertina altissima, respectively

Authors: Green, Benedict; Lee, Stephen; Davis, Thomas; Welch, Kevin

Submitted to: Toxicon: X
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/31/2019
Publication Date: 11/11/2019
Citation: Green, B.T., Lee, S.T., Davis, T.Z., Welch, K.D. 2019. Microsomal activation, and SH-SY5Y cell toxicity studies of tremetone and 6-hydroxytremetone isolated from rayless goldenrod Isocoma pluriflora and white snakeroot Agertina altissima, respectively. Toxicon: X. 5. https://doi.org/10.1016/j.toxcx.2019.100018.
DOI: https://doi.org/10.1016/j.toxcx.2019.100018

Interpretive Summary: It has been reported that tremetone found in white snakeroot (Ageratina altissima) and rayless goldenrod (Isocoma pluriflora), requires metabolism in order to be toxic. The purpose of this work was to compare the toxicity in two cell lines to determine if the actions of tremetone are concentration-dependent, and if metabolism by RLM is needed to activate tremetone. We show that tremetone is directly toxic without metabolism.

Technical Abstract: Tremetone is a putative toxin in white snakeroot and rayless goldenrod. The actions of tremetone and 6-hydroxytrematone were tested in B16 and SH-SY5Y cells and cytotoxicity measured with an MTT assay. Tremetone actions were not concentration-dependent in B16 cells. In SH-SY5Y cells, tremetone did not need microsomal activation to be cytotoxic in a concentration-dependent manner (P = 0.0011, concentration x treatment, two-way ANOVA; IC50 = 490 µM). 6-hydroxytrematone was not cytotoxic in SH-SY5Y cells.