Ferron Pierre-Jean, Dumazeau Kevin, Beaulieu Jean-François, Le Hégarat Ludovic, Fessard Valérie
Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health & Safety, Fougères 35300, France.
Laboratory of Intestinal Physiopathology, University of Sherbrooke, Sherbrooke, QC J1G 0A2, Canada.
Toxins (Basel). 2016 Feb 19;8(2):50. doi: 10.3390/toxins8020050.
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.
对海产品中的藻毒素进行监测是因为它们可导致人类食物中毒。藻毒素不仅单独存在，还会以混合物的形式存在于贝类中。本研究的目的是利用中性红摄取试验，在两种人类肠道细胞模型（Caco-2细胞和人肠上皮隐窝样细胞（HIEC））上评估欧洲常见的三种亲脂性藻毒素（冈田酸（OA）、岩沙海葵毒素（YTX）和azaspiracid-1（AZA-1））二元组合的体外毒性相互作用。基于单一毒素的细胞毒性，我们使用组合指数-等效线图方程研究二元混合物中毒素之间的相互作用，该方法在药理学中广泛用于研究药物相互作用。此方法将混合物中毒素之间的相互作用定量分类为协同、相加或拮抗。AZA-1/OA和YTX/OA混合物随着毒素浓度增加显示出越来越强的拮抗作用。相反，AZA-1/YTX混合物随着浓度增加显示出越来越强的协同作用，尤其是对于高YTX浓度的混合物。这些结果突出了AZA-1/YTX混合物在海产品中毒方面的危害潜力。
