title: Mycotoxins modify the barrier function of Caco-2 cells through differential gene expression of specific claudin isoforms: Protective effect of illite mineral clay.
abstract: Aflatoxin B1 (AFB1), fumonisin B1 (FB1), ochratoxin A (OTA) and T-2 toxin (T2) are mycotoxins that commonly contaminate the food chain and cause various toxicological effects. Their global occurrence is regarded as an important risk factor for human and animal health. In this study, the results demonstrate that, in human Caco-2 cells, AFB1, FB1, OTA and T2 origin cytotoxic effects, determining cell viability through MTT assay and LDH leakage, and decrease trans-epithelial electrical resistance (TEER). The decrease in barrier properties is concomitant with a reduction in the expression levels of the tight junction constituents claudin-3, claudin-4 and occludin. The protective effect of mineral clays (diosmectite, montmorillonite and illite) on alterations in cell viability and epithelial barrier function induced by the mycotoxins was also evaluated. Illite was the best clay to prevent the mycotoxin effects. Illite plus mycotoxin co-treatment completely abolished AFB1 and FB1-induced cytotoxicity. Also, the decreases in the gene expression of claudins and the reduction of TEER induced by mycotoxins were reversed by the illite plus mycotoxin co-treatment. In conclusion, these results demonstrated that mycotoxins AFB1, FB1, T2 and OTA disrupt the intestinal barrier permeability by a mechanism involving reduction of claudin isoform expressions, and illite counteracts this disruption.
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Romero
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Irma
authors.initials: I
authors.lastname: Ares
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Ramos
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Castellano
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: María-Rosa
authors.initials: MR
authors.lastname: Martínez-Larrañaga
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: aanadon@ucm.es.
authors.forename: Arturo
authors.initials: A
authors.lastname: Anadón
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: María-Aránzazu
authors.initials: MA
authors.lastname: Martínez
mesh_terms: D000931:Antidotes / Q000494:pharmacology; D001546:Bentonite / Q000494:pharmacology*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D062465:Claudin-3 / Q000235:genetics; D062506:Claudin-4 / Q000235:genetics; D017097:Electric Impedance; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008903:Minerals / Q000494:pharmacology*; D009183:Mycotoxins / Q000633:toxicity*; D062793:Occludin / Q000235:genetics; D010539:Permeability; D017640:Silicates / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects
chemical_list: D000931:Antidotes; D062465:Claudin-3; D062506:Claudin-4; D008903:Minerals; D009183:Mycotoxins; D062793:Occludin; D017640:Silicates; C099089:illite; D001546:Bentonite; C033214:Smectite
keywords: Barrier function; Caco-2-cells; Cytotoxicity; Illite; Mycotoxins; Tight junctions