Aflatoxin B1 and Aflatoxin M1 Induce Compromised Intestinal Integrity through Clathrin-Mediated Endocytosis

• Published in: Toxins Vol. 13; no. 3; p. 184
• Main Authors: Gao, Yanan, Bao, Xiaoyu, Meng, Lu, Liu, Huimin, Wang, Jiaqi, Zheng, Nan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02-03-2021; MDPI
• Subjects: Aflatoxin B1; Aflatoxin B1 - metabolism; Aflatoxin B1 - toxicity; Aflatoxin M1; Aflatoxin M1 - metabolism; Aflatoxin M1 - toxicity; Aflatoxins; Agricultural products; Animals; Caco-2 Cells; Cell differentiation; Cell Survival - drug effects; Cell viability; Chemical contaminants; Chlorpromazine; Clathrin; Clathrin - metabolism; Climate change; Contaminants; Dextran; Dextrans; Electric Impedance; Electrical resistivity; Endocytosis; Fluorescein; Fluorescein isothiocyanate; Food contamination & poisoning; Humans; Integrity; Internalization; Intestinal Absorption - drug effects; intestinal epithelial barrier; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine; Male; Medical research; Metabolism; Metabolites; Mice; Mice, Inbred ICR; Milk; Permeability; Proteins; Tight Junction Proteins - metabolism; Tight Junctions - drug effects; Tight Junctions - metabolism; Tight Junctions - pathology; Toxins; Villus; aflatoxin M1; intestinal epithelial barrier; endocytosis; aflatoxin B1
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins13030184

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.
, 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.
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.