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

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 flu...

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Main Authors: Yanan Gao, Songli Li, Jiaqi Wang, Chaochao Luo, Shengguo Zhao, Nan Zheng
Format: Article
Language:English
Published: MDPI AG 2017-12-01
Series:Toxins
Subjects:
Online Access:https://www.mdpi.com/2072-6651/10/1/13
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author Yanan Gao
Songli Li
Jiaqi Wang
Chaochao Luo
Shengguo Zhao
Nan Zheng
author_facet Yanan Gao
Songli Li
Jiaqi Wang
Chaochao Luo
Shengguo Zhao
Nan Zheng
author_sort Yanan Gao
collection DOAJ
description 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.
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spelling doaj.art-def4f394f226407a896dbac0dfbfc74b2022-12-22T02:57:20ZengMDPI AGToxins2072-66512017-12-011011310.3390/toxins10010013toxins10010013Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or CollectivelyYanan Gao0Songli Li1Jiaqi Wang2Chaochao Luo3Shengguo Zhao4Nan Zheng5Ministry 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, ChinaMinistry 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, ChinaMinistry 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, ChinaMinistry 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, ChinaMinistry 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, ChinaMinistry 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, ChinaAflatoxin 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.https://www.mdpi.com/2072-6651/10/1/13aflatoxin M1ochratoxin Aintestinal epithelial cellstight junctionpermeability
spellingShingle Yanan Gao
Songli Li
Jiaqi Wang
Chaochao Luo
Shengguo Zhao
Nan Zheng
Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively
Toxins
aflatoxin M1
ochratoxin A
intestinal epithelial cells
tight junction
permeability
title Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively
title_full Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively
title_fullStr Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively
title_full_unstemmed Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively
title_short Modulation of Intestinal Epithelial Permeability in Differentiated Caco-2 Cells Exposed to Aflatoxin M1 and Ochratoxin A Individually or Collectively
title_sort modulation of intestinal epithelial permeability in differentiated caco 2 cells exposed to aflatoxin m1 and ochratoxin a individually or collectively
topic aflatoxin M1
ochratoxin A
intestinal epithelial cells
tight junction
permeability
url https://www.mdpi.com/2072-6651/10/1/13
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