Antidote-like Effect of Cyclodextrins on Plant Neurotoxin Veratridine

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Veratridine (VTD) is a plant neurotoxin that acts by blocking the voltage-gated sodium channels (VGSC) of cell membranes. Symptoms of VTD intoxication include intense nausea, hypotension, arrhythmia, and loss of consciousness. The treatment for the intoxication is mainly focused on treating the symptoms, meaning there is no specific antidote against VTD.

It was successfully proven that inclusion complexes were formed between the alkaloid neurotoxin VTD and native β-CD and γ-CD as well as the anionic β-CD derivative SBCD. The equilibrium constants were estimated to be 1500 M−1, 7200 M−1 and 8200 M−1 for β-CD, γ-CD and SBCD, respectively, making the γ-CD and the anionic SBCD the most stable hosts. The 1H-NMR and 1H-1H ROESY experiments confirmed the incorporation of VTD in each of the CDs’ cavities and the most stable orientation of the molecule inside the CDs was elucidated by performing docking and molecular dynamics simulations. In vitro studies showed that the three studied CDs have antidote-like effects against the VTD toxicity, protecting Neuro-2a cell viability to different extent, depending on the CD type as well as the CD and VTD concentrations. 

Structure of ouabain (OB), a toxic cardiac glycoside that inhibits the Na+/K+ pump, added for the specific and sensitive detection of VTD, since it prevents cells from counteracting the increasing sodium intracellular concentrations produced by VTD exposure and VTD; and effect of VTD and OB in the Na+ cell transport.

Uribe, L.A.; Leonardo, S.; Nielsen, T.T.; Steinmann, C.; Campàs, M.; Fragoso, A. Supramolecular Complexes of Plant Neurotoxin Veratridine with Cyclodextrins and Their Antidote-like Effect on Neuro-2a Cell Viability. Pharmaceutics 202214, 598.

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