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Toxins 2018, 10(1), 13; https://doi.org/10.3390/toxins10010013

Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively

1,2,3,†
,
1,2,3,†
,
1,2,3
,
1,2,3
,
1,2,3
and
1,2,3,*
1
Ministry of Agriculture Laboratory of Quality & Safety Control for Risk Assessment for Dairy Products (Beijing), Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
2
Ministry of Agriculture-Milk and Dairy Product Inspection Center, Beijing 100193, China
3
State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
These authors contributed equally to the work.
*
Author to whom correspondence should be addressed.
Received: 10 November 2017 / Revised: 23 December 2017 / Accepted: 25 December 2017 / Published: 27 December 2017
(This article belongs to the Special Issue Effects of Mycotoxins on the Intestine)
View Full-Text   |   Download PDF [3450 KB, uploaded 27 December 2017]   |  

Abstract

Aflatoxin M1 (AFM1) and ochratoxin A (OTA) are mycotoxins commonly found in milk; however, their effects on intestinal epithelial cells have not been reported. In the present study, we show that AFM1 (0.12 and 12 μM) and OTA (0.2 and 20 μM) individually or collectively increased the paracellular flux of lucifer yellow and fluorescein isothiocyanate (FITC)-dextrans (4 and 40 kDa) and decreased transepithelial electrical resistance values in differentiated Caco-2 cells after 48 h of exposure, indicating increased epithelial permeability. Immunoblotting and immunofluorescent analysis revealed that AFM1, OTA, and their combination decreased the expression levels of tight junction (TJ) proteins and disrupted their structures, namely, claudin-3, claudin-4, occludin, and zonula occludens-1 (ZO-1), and p44/42 mitogen-activated protein kinase (MAPK) partially involved in the mycotoxins-induced disruption of intestinal barrier. The effects of a combination of AFM1 and OTA on intestinal barrier function were more significant (p < 0.05) than those of AFM1 and OTA alone, yielding additive or synergistic effects. The additive or synergistic effects of AFM1 and OTA on intestinal barrier function might affect human health, especially in children, and toxin risks should be considered. View Full-Text
Keywords: aflatoxin M1; ochratoxin A; intestinal epithelial cells; tight junction; permeability aflatoxin M1; ochratoxin A; intestinal epithelial cells; tight junction; permeability
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Gao, Y.; Li, S.; Wang, J.; Luo, C.; Zhao, S.; Zheng, N. Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively. Toxins 2018, 10, 13.

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