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Journal Articles Toxins Year : 2021

Permeability of the Cyanotoxin Microcystin-RR across a Caco-2 Cells Monolayer

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Jérôme Henri
Rachelle Lanceleur
  • Function : Author
  • PersonId : 1102711
Jean-Michel Delmas
  • Function : Author
  • PersonId : 961013
Valérie Fessard
  • Function : Author
  • PersonId : 881770
Antoine Huguet
  • Function : Author
  • PersonId : 926901

Abstract

Microcystins (MCs) are toxins produced by several cyanobacterial species found worldwide. While MCs have a common structure, the variation of two amino acids in their structure affects their toxicity. As toxicodynamics are very similar between the MC variants, their differential toxicity could rather be explained by toxicokinetic parameters. Microcystin-RR (MC-RR) is the second most abundant congener and induces toxicity through oral exposure. As intestinal permeability is a key parameter of oral toxicokinetics, the apparent permeability of MC-RR across a differentiated intestinal Caco-2 cell monolayer was investigated. We observed a rapid and large decrease of MC-RR levels in the donor compartment. However, irrespective of the loaded concentration and exposure time, the permeabilities were very low from apical to basolateral compartments (from 4 to 15 × 10−8 cm·s−1) and from basolateral to apical compartments (from 2 to 37 × 10−8 cm·s−1). Our results suggested that MC-RR would be poorly absorbed orally. As similar low permeability was reported for the most abundant congener microcystin-LR, and this variant presented a greater acute oral toxicity than MC-RR, we concluded that the intestinal permeability was probably not involved in the differential toxicity between them, in contrast to the hepatic uptake and metabolism.
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anses-03266193 , version 1 (21-06-2021)

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Attribution - CC BY 4.0

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Jérôme Henri, Rachelle Lanceleur, Jean-Michel Delmas, Valérie Fessard, Antoine Huguet. Permeability of the Cyanotoxin Microcystin-RR across a Caco-2 Cells Monolayer. Toxins, 2021, 13 (3), pp.178. ⟨10.3390/toxins13030178⟩. ⟨anses-03266193⟩

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