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

Yanan Gao,Nan Zheng,Huimin Liu,Lu Meng,Jiaqi Wang,Xiaoyu Bao

doi:10.3390/toxins13030184

Abstract

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. In vivo, 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. In vitro 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.

Highlights

In high humidity and warm environmental temperatures, crops such as corn, peanut, and wheat are highly likely to encounter air-borne or insect-borne contamination of toxigenic fungi and their mycotoxins during growth and harvest [1]
There is evidence that over 25% of agricultural products worldwide are contaminated by mycotoxins, and their intake represents the major source of exposure [2]
The objectives of the present study were to evaluate the combined toxicity of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) on the intestinal barrier and on mechanisms involved in dysfunction in both in vivo and in vitro models

Summary

Introduction

In high humidity and warm environmental temperatures, crops such as corn, peanut, and wheat are highly likely to encounter air-borne or insect-borne contamination of toxigenic fungi (molds) and their mycotoxins during growth and harvest [1]. There is evidence that over 25% of agricultural products worldwide are contaminated by mycotoxins, and their intake represents the major source of exposure [2]. In the 25 to 50 years, it is expected that the concentration of CO2 in the atmosphere will double or triple, and the temperature will rise by 2 to 5 ◦C. This will increase the frequency of droughts and promote plant stress, which is likely to affect the production of secondary metabolites, especially mycotoxins [5]

Objectives

Methods

Results