Aflatoxin B1 and Aflatoxin M1 Induce Compromised Intestinal Integrity through Clathrin-Mediated Endocytosis.
Aflatoxin B1 and Aflatoxin M1 Induce Compromised Intestinal Integrity through Clathrin-Mediated Endocytosis.
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DOI：
10.3390/toxins13030184
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发表时间：
2021-03-02
期刊：
影响因子：
4.2
通讯作者：
Zheng N
中科院分区：
文献类型：
--
作者：
Gao Y;Bao X;Meng L;Liu H;Wang J;Zheng N
随着饮食的日益多样化和复杂化，人类面临着同时暴露于黄曲霉毒素B1（AFB 1）和黄曲霉毒素M1（AFM 1）的风险，这是全球乳制品和其他农产品中众所周知的污染物。肠道是抵抗外部污染物的第一道屏障;然而，关于AFB 1和AFM 1对肠道完整性的联合作用的证据缺乏。在体内，暴露于0.3 mg/kg b.w.的小鼠中，与肠屏障功能相关的血清生化参数、绒毛高度/隐窝深度比以及claudin-1和闭合小带-1的分布模式受到显著影响。黄曲霉毒素B1和3.0 mg/kg b.w. AFM1。对分化的Caco-2细胞的体外研究结果表明，单独和组合的AFB 1（0.5和4 μg/mL）和AFM 1（0.5和4 μg/mL）降低细胞活力和跨上皮电阻值，并以剂量依赖性方式增加异硫氰酸荧光素-葡聚糖的细胞旁渗透性。此外，AFM 1加重了AFB 1诱导的肠屏障受损，表现为紧密连接蛋白的下调及其再分布，特别是内化。添加抑制剂氯丙嗪说明网格蛋白介导的内吞作用部分导致了肠道完整性受损。协同效应和累加效应是主要的相互作用，表明这些毒素可能对人类健康产生负面影响。
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 μg/mL) and AFM1 (0.5 and 4 μg/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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影响因子：
6.1
作者：
Akbari P;Braber S;Varasteh S;Alizadeh A;Garssen J;Fink-Gremmels J
通讯作者：
Fink-Gremmels J
影响因子：
4.4
作者：
Gratz, S.;Wu, Q. K.;Turner, P. C.
通讯作者：
Turner, P. C.
影响因子：
3
作者：
Akinrinmade, Fadeyemi Joseph;Akinrinde, Akinleye Stephen;Amid, Adetayo
通讯作者：
Amid, Adetayo
影响因子：
3
作者：
Akinrinde, Akinleye Stephen;Ogunbunmi, Temitope;Akinrinmade, Fadeyemi Joseph
通讯作者：
Akinrinmade, Fadeyemi Joseph
影响因子：
6.3
作者：
Crenn, Pascal;Messing, Bernard;Cynober, Luc
通讯作者：
Cynober, Luc