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Permeability of dihydro- and cysteine-brevetoxin metabolites across a Caco-2 cell monolayer

Abstract : Brevetoxin B is a highly reactive molecule, due in part to an α,β-unsaturated aldehyde group at the terminal side chain, leading to metabolism by reduction, oxidation and conjugation. These reactions have little effect to reduce intrinsic activity at the voltage-gated sodium channel or during toxicity testing by either enzyme-linked immunosorbent assay or mouse bioassay. Here we investigate the potential for intestinal absorption of the two most abundant brevetoxins present in Gulf of Mexico oysters using human Caco-2 cell monolayers, a widely utilized in vitro test to predict oral bioavailability of drugs and their metabolites. We found that both dihydrobrevetoxin B and cysteine brevetoxin B were rapidly taken up by the Caco-2 monolayer. However, only dihydrobrevetoxin B passes through the monolayer to reach the basal compartment. Dihydrobrevetoxin B has a moderate apparent permeability coefficient of 1.6×10-6cm/s at 500ng/mL and nearly 50% of the toxin passes from the apical to basal compartment in 24h. The inability of the cysteine brevetoxin B to pass through an intestinal epithelial barrier suggests that this bioactive brevetoxin metabolite that persists in shellfish may not contribute to neurotoxic shellfish poisoning.
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https://hal-anses.archives-ouvertes.fr/hal-00998117
Contributor : Emmanuelle Chiffoleau Connect in order to contact the contributor
Submitted on : Friday, May 30, 2014 - 3:00:51 PM
Last modification on : Friday, October 8, 2021 - 4:06:02 PM

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Jérôme Henri, Ta Leighfield, Rachelle Lanceleur, Antoine Huguet, Js Ramsdell, et al.. Permeability of dihydro- and cysteine-brevetoxin metabolites across a Caco-2 cell monolayer. Harmful Algae, Elsevier, 2014, 32, pp.22-26. ⟨10.1016/j.hal.2013.11.007⟩. ⟨hal-00998117⟩

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