Aflatoxin B1 and Aflatoxin M1 Induce Compromised Intestinal Integrity through Clathrin-Mediated Endocytosis

文献类型： 外文期刊

第一作者： Gao, Yanan

作者： Gao, Yanan;Bao, Xiaoyu;Meng, Lu;Liu, Huimin;Wang, Jiaqi;Zheng, Nan;Gao, Yanan;Bao, Xiaoyu;Meng, Lu;Liu, Huimin;Wang, Jiaqi;Zheng, Nan;Gao, Yanan;Bao, Xiaoyu;Meng, Lu;Liu, Huimin;Wang, Jiaqi;Zheng, Nan;Gao, Yanan;Bao, Xiaoyu;Meng, Lu;Liu, Huimin;Wang, Jiaqi;Zheng, Nan

作者机构：

关键词： aflatoxin B1; aflatoxin M1; intestinal epithelial barrier; endocytosis

期刊名称：TOXINS （ 影响因子：3.531； 五年影响因子：3.832 ）

ISSN：

年卷期： 2021 年 13 卷 3 期

页码：

收录情况： SCI

摘要： With the growing diversity and complexity of diet, humans are at risk of simultaneous exposure to aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1), which are well-known contaminants in dairy and other agricultural products worldwide. The intestine represents the first barrier against external contaminants; however, evidence about the combined effect of AFB1 and AFM1 on intestinal integrity is lacking. In vivo, the serum biochemical parameters related to intestinal barrier function, ratio of villus height/crypt depth, and distribution pattern of claudin-1 and zonula occluden-1 were significantly affected in mice exposed to 0.3 mg/kg b.w. AFB1 and 3.0 mg/kg b.w. AFM1. In vitro results on differentiated Caco-2 cells showed that individual and combined AFB1 (0.5 and 4 mu g/mL) and AFM1 (0.5 and 4 mu g/mL) decreased cell viability and trans-epithelial electrical resistance values as well as increased paracellular permeability of fluorescein isothiocyanate-dextran in a dose-dependent manner. Furthermore, AFM1 aggravated AFB1-induced compromised intestinal barrier, as demonstrated by the down-regulation of tight junction proteins and their redistribution, particularly internalization. Adding the inhibitor chlorpromazine illustrated that clathrin-mediated endocytosis partially contributed to the compromised intestinal integrity. Synergistic and additive effects were the predominant interactions, suggesting that these toxins are likely to have negative effects on human health.

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