Determination of intestinal absorption of the paralytic shellfish toxin GTX-5 using the Caco-2 human cell model
2021
Rodrigues, Elsa T. | Nascimento, Susana F. | Pires, Cristiana L. | Godinho, Lia P. | Churro, Catarina | Moreno, Maria João | Pardal, Miguel A.
Contributing to the human health risk assessment, the present study aims to evaluate the ability of paralytic shellfish toxins (PSTs) to cross the human intestinal epithelium by using the Caco-2 permeability assay. A crude extract prepared from the PST producer dinoflagellate Gymnodinium catenatum strain, GCAT1_L2_16, and the PST analogue gonyautoxin-5 (GTX-5) prepared from a certified reference material (CRM) were tested. In the conditions of the assay, none of the compounds altered Caco-2 viability, or the integrity of cell monolayers. The GTX-5 apparent permeability coefficients are 0.9×10⁻⁷ and 0.6×10⁻⁷ cm s⁻¹ for the crude extract and CRM, respectively, thus, <10⁻⁶ cm s⁻¹, which indicates that humans absorb this PST analogue poorly. The present study also reveals that, during a 90-min exposure, GTX-5 is not metabolised to a high extent by Caco-2 or retained in the Caco-2 cytoplasm. Since it is known that GTX-5 can be found in the spleen, liver or kidney of the victims, as well as in the urine samples of patients who consumed contaminated seafood, further research is needed to clarify the transport mechanisms involved, permeation time and dose-dependence, and the possible role of intestinal microflora.
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