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Toxicol Lett. 2019 Jul;309:1-9. doi: 10.1016/j.toxlet.2019.03.010. Epub 2019 Mar 20.

Modulation of intestinal epithelial permeability and mucin mRNA (MUC2, MUC5AC, and MUC5B) expression and protein secretion in Caco-2/HT29-MTX co-cultures exposed to aflatoxin M1, ochratoxin A, and zearalenone individually or collectively.

Author information

1
Ministry of Agriculture-Key Laboratory of Quality & Safety Control for Milk and Dairy Products, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China; Ministry of Agriculture-Laboratory of Quality and Safety Risk Assessment for Dairy Products, Beijing, PR China; Ministry of Agriculture-Milk and Dairy Product Inspection Center, Beijing 100193, PR China; State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China.
2
Ministry of Agriculture-Key Laboratory of Quality & Safety Control for Milk and Dairy Products, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China; Ministry of Agriculture-Laboratory of Quality and Safety Risk Assessment for Dairy Products, Beijing, PR China; Ministry of Agriculture-Milk and Dairy Product Inspection Center, Beijing 100193, PR China; State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, PR China. Electronic address: zhengnan_1908@126.com.

Abstract

Aflatoxin M1 (AFM1), ochratoxin A (OTA), and zearalenone (ZEA) are mycotoxins commonly found in milk. Mycotoxin contamination has caused food safety concerns worldwide since most of the toxic effects in humans are serious. The combined toxic effects of these mycotoxins on intestinal epithelial cells have not been reported. Herein, we investigated the combined effects of AFM1, OTA, and ZEA on intestinal integrity and define the underlying mechanisms(s) of their effects in Caco-2/HT29-MTX co-cultures. Our results showed that the mixtures of AFM1 + OTA, AFM1 + ZEA, and AFM1 + ZEA + OTA significantly increased epithelial permeability. Immunofluorescence analysis and transmission electron microscopy revealed that mycotoxins altered TJ proteins morphology and disrupted their structures. Also, the present study showed that mixtures of mycotoxins significantly modulated MUC5AC and MUC5B mRNA levels and protein secretion. This study demonstrated that the effects of mixtures of mycotoxins on intestinal barrier function were more significant than AFM1 alone. More importantly, the damage of intestinal integrity caused by mycotoxins was correlated to the change of the TJ proteins location and the decrease of mucin secretion. Mixtures of AFM1, OTA, and ZEA in food might pose a health risk to consumers, particularly in children, and toxin risks should be considered.

KEYWORDS:

Aflatoxin M1; Caco-2/HT29-MTX co-cultures; Mucin; Ochratoxin A; Tight junction; Zearalenone

PMID:
30904571
DOI:
10.1016/j.toxlet.2019.03.010
[Indexed for MEDLINE]

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