Submitted to: Poisoning by Plants, Mycotoxins, and Related Toxins
Publication Type: Book / Chapter
Publication Acceptance Date: 5/21/2010
Publication Date: 5/1/2011
Citation: Green, B.T., Lee, S.T., Welch, K.D., Panter, K.E., Kem, W. 2011. Determination of the relative toxicity of enantiomers with cell-based assays. In: Riet-Correa, F., Pfister, J., Schild, A.L., Wierenga, T., editors. Poisoning by Plants, Mycotoxins, and Related Toxins. Cambridge, MA. CAB International. 100:581-7.
Interpretive Summary: Many bioactive compounds produced by plants exhibit chirality or "handedness". Chirality is a type of molecular asymmetry where two forms of the same molecule exist as non-superimposable mirror images of each other. The alternate forms of the molecule are termed enantiomers that experimentally, have the ability to rotate plane polarized light in opposite directions. Current estimations of plant toxicities are based on total toxin levels without considering sterochemistry. However, if the predominant enantiomer found in a plant is of a less potent form then the overall toxicity of the plant will be overestimated. This work establishes that cell culture based assays may correlate with the relative toxicity of some enantiomers in mice.
Technical Abstract: There is an important need to determine the relative biological effects of toxin enantiomers found in poisonous plants. Current estimations of plant toxicities are based on total toxin levels without considering stereochemistry. However, if the predominant enantiomer found in a plant is of a less toxic form then the overall toxicity of the plant will be overestimated. Coniine, a toxin found in poison hemlock (Conium maculatum) is present as two optically active forms. Results from an assay using TE-671 cells which express human fetal nicotinic acetylcholine receptors and a mouse bioassay support the importance of considering enantiomers when determining plant toxicity. In the cell-based assay, coniine had rank order of potency of (-)-, (±)-, and (+)- coniine. In a mouse bioassay, the order of toxicity for the coniine enantiomers was the same. Similar patterns of toxicities were observed for enantiomers of ammodendrine and anabasine isolated from Nicotinana glauca and Lupinus formosus respectively. This work establishes that in vitro relative potencies of enantiomers can directly correlate with the relative toxicity of the enantiomers in mice. Consequently, cell-based assays can play an important role in the estimation of the effects of plant toxins. Moreover, the possibility of stereochemical interactions should be considered when determining the overall toxicity of poisonous plants.