Abstract
Aflatoxin M1 (AFM1) is a mycotoxin that is commonly found as a milk contaminant, and its presence in milk has been linked to cytotoxicity. The present study aimed to evaluate the acute cytotoxic effects of AFM1 on intestinal Caco-2 cells. Initially, we checked the morphology and viability of Caco-2 cells after treatment with different concentrations of AFM1 (5 ng/L, 50 ng/L, 250 ng/L, 500 ng/L, 1000 ng/L, and 2000 ng/L) for different time intervals (6 h, 12 h, and 24 h). It was found that AFM1 did not show any effect on cell morphology, but 10% decrease in viability above 1000 ng/L after 12 h. Furthermore, DCFDA assay showed increased ROS production after 6 h treatments. qPCR analysis showed an increased expression of epithelial-specific cytoskeleton marker genes, Cytokeratin, Villin, Vimentin, and JAM-1, and a decreased expression of tight junction protein genes, Claudin-1, Occludin, and ZO-1. Similarly, we found an increased expression of Cyp1a1 transcript with an increasing AFM1 concentration and incubation time. This gene expression analysis showed AFM1 can cause disruption of tight junctions between intestinal cells, which was further confirmed by a transwell experiment. In conclusion, consumption of AFM1-contaminated milk does not show any effect on cells morphology and viability but decreases the expression of intestinal barrier transcripts that may lead to the disruption of intestinal barrier function and leaky gut.
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1. The Director of ICAR-NDRI, provided the infrastructure and scholar fellowships to carry out the present study.
2. The Director of ICAR-NDRI, provided the infrastructure and scholar fellowships to carry out the present study. The Department of Biotechnology, Ministry of Science and Technology, India (Grant No. 102/IFD/SAN/3670/2014–15), and the Indian Council of Agricultural Research-National Agricultural Science Fund (NASF) project (File No. NASF/ABA-7006/2018-19/199) provided financial support to conduct this work.
3. The Indian Council of Medical Research (ICMR) awarded the Senior Research Fellow scholarship to Lal Krishan Kumar (Project file No. 45/23/2019-Toxi/BMS) and Surya Kant Verma (Project file No. RBMH/FW/2020/23).
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Dr. Suneel Kumar Onteru, Dr. Dheer Singh, and Dr. Rajni Kumar Paul conceived the idea and organized the present study. Lal Krishan Kumar, Surya Kant Verma, Rajeev Chandel, and Meet Thumar conducted experiments. Lal Krishan Kumar and Surya Kant Verma performed data analysis and wrote the manuscript. Suneel Kumar Onteru corrected the manuscript, and Rajni Kumar Paul, Surya Kant Verma, and Meet Thumar edited the manuscript.
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Kumar, L.K., Verma, S.K., Chandel, R. et al. Aflatoxin M1 decreases the expression of genes encoding tight junction proteins and influences the intestinal epithelial integrity. Mycotoxin Res 39, 453–467 (2023). https://doi.org/10.1007/s12550-023-00505-2
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DOI: https://doi.org/10.1007/s12550-023-00505-2