School of Food Science and Technology, International Joint Laboratory on Food Safety, Synergetic Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
Yixing Institute of Food and Biotechnology Co., Ltd, Yixing, Jiangsu 214200, PR China.
J Agric Food Chem. 2024 Apr 10;72(14):8214-8224. doi: 10.1021/acs.jafc.4c01888. Epub 2024 Apr 1.
The emerging mycotoxins enniatins (ENNs) and the traditional mycotoxin deoxynivalenol (DON) often co-contaminate various grain raw materials and foods. While the liver is their common target organ, the mechanism of their combined effect remains unclear. In this study, the combined cytotoxic effects of four ENNs (ENA, ENA, ENB, and ENB) with DON and their mechanisms were investigated using the HepG2 cell line. Additionally, a population exposure risk assessment of these mycotoxins was performed by using experiments and computer simulations. The results showed that only ENA at 1/4 IC and ENB at 1/8 IC coexposed with DON showed an additive effect, while ENB showed the strongest antagonism at IC (CI = 3.890). Co-incubation of ENNs regulated the signaling molecule levels which were disrupted by DON. Transcriptome analysis showed that ENB (IC) up-regulated the PI3K/Akt/FoxO signaling pathway and inhibited the expression of apoptotic genes (Bax, P53, Caspase 3, etc.) via phosphorylation of FoxO, thereby reducing the cytotoxic effects caused by DON. Both types of mycotoxins posed serious health risks, and the cumulative risk of coexposure was particularly important for emerging mycotoxins.
新型霉菌毒素恩镰菌素（ENNs）和传统霉菌毒素脱氧雪腐镰刀菌烯醇（DON）经常共同污染各种谷物原料和食品。虽然肝脏是它们的常见靶器官，但它们联合作用的机制尚不清楚。在这项研究中，使用 HepG2 细胞系研究了四种 ENNs（ENA、ENA、ENB 和 ENB）与 DON 的联合细胞毒性作用及其机制。此外，还通过实验和计算机模拟对这些霉菌毒素的人群暴露风险进行了评估。结果表明，只有 ENA 在 1/4 IC 和 ENB 在 1/8 IC 与 DON 共同暴露时表现出相加作用，而 ENB 在 IC 时表现出最强的拮抗作用（CI = 3.890）。ENNs 的共孵育调节了 DON 破坏的信号分子水平。转录组分析表明，ENB（IC）通过 FoxO 的磷酸化，上调了 PI3K/Akt/FoxO 信号通路，并抑制了凋亡基因（Bax、P53、Caspase 3 等）的表达，从而减轻了 DON 引起的细胞毒性作用。这两种霉菌毒素都对健康构成严重威胁，而共同暴露的累积风险对新型霉菌毒素尤为重要。
