title: Combined Effects of Lipophilic Phycotoxins (Okadaic Acid, Azapsiracid-1 and Yessotoxin) on Human Intestinal Cells Models.
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.
authors.affiliation: Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health &amp; Safety, Fougères 35300, France. ferron.pj@gmail.com.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Ferron
authors.affiliation: Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health &amp; Safety, Fougères 35300, France. kevin.dumazeau@gmail.com.
authors.forename: Kevin
authors.initials: K
authors.lastname: Dumazeau
authors.affiliation: Laboratory of Intestinal Physiopathology, University of Sherbrooke, Sherbrooke, QC J1G 0A2, Canada. jean-francois.beaulieu@usherbrooke.ca.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Beaulieu
authors.affiliation: Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health &amp; Safety, Fougères 35300, France. ludovic.lehegarat@anses.fr.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Le Hégarat
authors.affiliation: Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health &amp; Safety, Fougères 35300, France. valerie.fessard@anses.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Fessard
mesh_terms: D018938:Caco-2 Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D005506:Food Contamination; D006801:Humans; D008387:Marine Toxins / Q000633:toxicity*; D008978:Mollusk Venoms; D009499:Neutral Red / Q000378:metabolism; D019319:Okadaic Acid / Q000633:toxicity*; D035964:Oxocins / Q000633:toxicity*; D017747:Seafood; D013141:Spiro Compounds / Q000633:toxicity*; D000095702:Polyether Toxins
chemical_list: D008387:Marine Toxins; D008978:Mollusk Venoms; D009499:Neutral Red; D019319:Okadaic Acid; D035964:Oxocins; D013141:Spiro Compounds; C406592:azaspiracid; D000095702:Polyether Toxins; C066632:yessotoxin
keywords: cytotoxicity; enterocytes; lipophilic phycotoxins; mixtures