ENVT, INP, UMR1331, Toxalim Research Centre in Food Toxicology, Université de Toulouse, 31076, Toulouse, France,
Arch Toxicol. 2013 Dec;87(12):2233-41. doi: 10.1007/s00204-013-1067-8. Epub 2013 May 7.
Enniatins, the most prevalent emerging mycotoxins, represent an emerging food safety issue, because of their common co-occurrence with other fusariotoxins such as trichothecenes co-produced by Fusarium spp on field grains and because of their extensive prevalence in grains. In this study, the intestinal toxicity of enniatin B1 (ENN) alone and mixed with the most toxic trichothecene T-2 toxin (T2) was characterized by using two biological models from pig, the most sensitive species: the intestinal cell line IPEC1 (in vitro exposure) and jejunal explants (ex vivo exposure). Dose-dependent decreases in cell proliferation in IPEC1 and in the histopathological scores of explants were observed for ENN at μM-levels and for T2 at nM-levels, with IC50 values for ENN of 15.8 and 29.7 μM, and for T2 of 9.3 and 15.1 nM in vitro and ex vivo, respectively. Interaction analysis by probabilistic and by determinist approaches showed a less than additive effect both in vitro and ex vivo, at IC50 values, with increasing antagonism with decreasing concentrations of toxins. The results obtained by the determinist median-effect dose analysis and by the nonlinear regression analysis were concordant. All the median-effect doses estimated for IPEC cells were included in the IC50 confidence intervals of the nonlinear regression fitting. Given the occurrence of enniatins, potential synergy following the co-occurrence of enniatins and the major fusariotoxins, especially trichothecene B deoxynivalenol should be investigated.
恩镰菌素是最常见的新兴霉菌毒素,是一个新兴的食品安全问题,因为它们与其他镰刀菌毒素(如由镰刀菌属在田间谷物上共同产生的三萜烯)共同存在,并且在谷物中广泛存在。在这项研究中,使用来自猪的两种生物模型(最敏感的物种):肠细胞系 IPEC1(体外暴露)和空肠外植体(离体暴露),来表征恩镰菌素 B1(ENN)单独存在和与最毒的三萜烯 T-2 毒素(T2)混合存在时的肠道毒性。在 μM 水平上观察到 ENN 在 IPEC1 中细胞增殖减少和在离体外植体中的组织病理学评分降低,在 nmol 水平上观察到 T2 减少,ENN 的 IC50 值分别为 15.8 和 29.7 μM,T2 的 IC50 值分别为 9.3 和 15.1 nM 在体外和离体。通过概率和确定性方法的相互作用分析表明,在 IC50 值下,无论是在体外还是在离体,都存在低于相加的效应,随着毒素浓度的降低,拮抗作用增加。通过确定性中值效应剂量分析和非线性回归分析得到的结果是一致的。所有估计的 IPEC 细胞的中值效应剂量都包含在非线性回归拟合的 IC50 置信区间内。考虑到恩镰菌素的存在,应该研究恩镰菌素和主要镰刀菌毒素(尤其是三萜烯脱氧雪腐镰刀菌烯醇)共存时的潜在协同作用。