Combined Effects of Lipophilic Phycotoxins (Okadaic Acid, Azapsiracid-1 and Yessotoxin) on Human Intestinal Cells Models.

Pierre-Jean Ferron,Kevin Dumazeau,Ludovic Le Hégarat,Valérie Fessard,Jean-François Beaulieu

doi:10.3390/toxins8020050

Pierre-Jean Ferron, Kevin Dumazeau + Show 3 more

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https://doi.org/10.3390/toxins8020050

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Abstract

Phycotoxins are monitored in seafood because they can cause food poisonings in humans. Phycotoxins do not only occur singly but also as mixtures in shellfish. The aim of this study was to evaluate the in vitro toxic interactions of binary combinations of three lipophilic phycotoxins commonly found in Europe (okadaic acid (OA), yessotoxin (YTX) and azaspiracid-1 (AZA-1)) using the neutral red uptake assay on two human intestinal cell models, Caco-2 and the human intestinal epithelial crypt-like cells (HIEC). Based on the cytotoxicity of individual toxins, we studied the interactions between toxins in binary mixtures using the combination index-isobologram equation, a method widely used in pharmacology to study drug interactions. This method quantitatively classifies interactions between toxins in mixtures as synergistic, additive or antagonistic. AZA-1/OA, and YTX/OA mixtures showed increasing antagonism with increasing toxin concentrations. In contrast, the AZA-1/YTX mixture showed increasing synergism with increasing concentrations, especially for mixtures with high YTX concentrations. These results highlight the hazard potency of AZA-1/YTX mixtures with regard to seafood intoxication.

Highlights

Phycotoxins are secondary metabolites produced by some phytoplanktonic unicellular algae.Due to their accumulation in filtering shellfish, several acute food intoxications following human consumption of contaminated shellfish have been well documented [1]
human intestinal epithelial crypt-like cells (HIEC) and Caco-2 cells were exposed to phycotoxins okadaic acid (OA), AZA-1 and YTX for 24 h
YTX toxicity on the two cell types were similar, but AZA-1 IC50 values were significantly different in HIEC and Caco-2 cells, with a greater effect observed on Caco-2 cells

Summary

Introduction

Phycotoxins are secondary metabolites produced by some phytoplanktonic unicellular algae Due to their accumulation in filtering shellfish, several acute food intoxications following human consumption of contaminated shellfish have been well documented [1]. OA and its analogs, the dinophysistoxins, are polyethers responsible for the diarrhetic shellfish poisoning (DSP), causing symptoms such as nausea, severe diarrhea and abdominal pain [4]. These toxins are found worldwide and are protein phosphatase (PP) inhibitors AZAs are composed of a spiro-ring assembly, a cyclic amino group and a carboxylic function They are responsible for azaspiracid poisoning (AZP) [6] with

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