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Toxins (Basel). 2016 Feb 19;8(2):50. doi: 10.3390/toxins8020050.

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

Author information

1
Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health & Safety, Fougères 35300, France. ferron.pj@gmail.com.
2
Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health & Safety, Fougères 35300, France. kevin.dumazeau@gmail.com.
3
Laboratory of Intestinal Physiopathology, University of Sherbrooke, Sherbrooke, QC J1G 0A2, Canada. jean-francois.beaulieu@usherbrooke.ca.
4
Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health & Safety, Fougères 35300, France. ludovic.lehegarat@anses.fr.
5
Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health & Safety, Fougères 35300, France. valerie.fessard@anses.fr.

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.

KEYWORDS:

cytotoxicity; enterocytes; lipophilic phycotoxins; mixtures

PMID:
26907345
PMCID:
PMC4773803
DOI:
10.3390/toxins8020050
[Indexed for MEDLINE]
Free PMC Article

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