Mycotoxins modify the barrier function of Caco-2 cells through differential gene expression of specific claudin isoforms: Protective effect of illite mineral clay

Romero, Alejandro; Arés, Irma; Ramos, Eva; Castellano, V.; Martínez, Marta; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Martínez, María-Aránzazu

doi:10.1016/j.tox.2016.05.003

Cited by 91 publications

(81 citation statements)

References 79 publications

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“…After 24 h of the beginning of the test, TEER profiles of both samples were restored to primitive values meaning the recovery of the integrity of the cell monolayer. These results supported the protective effect of silicate‐based carriers in restoring the epithelial barrier of Caco‐2 cells by means of TEER measurements …”

Section: Discussionsupporting

confidence: 81%

“…These results supported the protective effect of silicate-based carriers in restoring the epithelial barrier of Caco-2 cells by means of TEER measurements. 46 Fluorescent microphotographs revealed the internalization of INH when loaded in the nanohybrid which was non observable in the case of free INH. In the cell substrate treated with INH-loaded HLNTs, it can be noticed that there was a blue signal due to INH present in the cell substrate, to indicate an actual internalization of the drug (no blue signal was present in the control).…”

Section: Discussionmentioning

confidence: 99%

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Halloysite nanotubes as tools to improve the actual challenge of fixed doses combinations in tuberculosis treatment

Carazo

Sandri

Cerezo

et al. 2019

J Biomedical Materials Res

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Halloysite nanotubes (HLNTs) were used as nanocarriers of the tuberculostatic agent isoniazid (INH), a BCS (Biopharmaceutics Classification System) class III drug. Self‐assembling nanohybrids (INH‐loaded HLNTs) with an average outer diameter of 90 nm and polydispersity index of 0.7 approximately, were obtained by spontaneous adsorption of INH molecules to HLNTs powder in aqueous medium. The nanohybrids were aimed to improve oral drug bioavailability and reduce physicochemical incompatibility of INH with other concomitantly administered tuberculostatic agents. In vitro drug release from INH‐loaded HLNTs was successfully fitted to a diffusive kinetic law founded on the adsorption–desorption equilibrium between drug molecules in solution and solid inorganic excipients. INH‐loaded HLNTs showed good in vitro biocompatibility toward Caco‐2 cells at the concentrations studied (up to 1233 μg/mL), with improved cell proliferation. Permeability tests showed that INH transport across Caco‐2 cellular membranes was greatly enhanced and fluorescent microscopy confirmed that the drug encapsulated into nanohybrid was effectively internalized by the cells. INH‐loaded HLNTs enhanced stability of the drug in presence of other tuberculostatic agents, both in binary and quaternary combinations. It has been demonstrated that simple interaction between INH with HLNTs leads to drug permeability and stability improvements that could greatly facilitate the design of multiple drug dosage forms, an actual challenge in oral treatment of tuberculosis. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Halloysite nanotubes as tools to improve the actual challenge of fixed doses combinations in tuberculosis treatment

Carazo

Sandri

Cerezo

et al. 2019

J Biomedical Materials Res

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“…Thus, we herein present the first investigation of the effect of such metabolites on intestinal barrier integrity of intestinal porcine epithelial cells. Such effects are well documented for the trichothecene mycotoxin DON [11,15,87,88,89], as well as for aflatoxins [90,91], zearalenone [92,93], ochratoxin A [94,95], patulin [96,97], fumonisin B1 [98,99,100] and T2 toxin [16,101]. Similarities with the original in vivo cell tissue and with humans and the fact that pigs are the most susceptible species to Fusarium mycotoxin DON, make porcine cell lines a highly suitable option for in vitro analysis of intestinal barrier integrity [102].…”

Section: Discussionmentioning

confidence: 99%

Effect of Fusarium-Derived Metabolites on the Barrier Integrity of Differentiated Intestinal Porcine Epithelial Cells (IPEC-J2)

Springler

Vrubel²,

Mayer³

et al. 2016

Toxins

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The human, animal and plant pathogen Fusarium, which contaminates agricultural commodities worldwide, produces numerous secondary metabolites. An example is the thoroughly-investigated deoxynivalenol (DON), which severely impairs gastrointestinal barrier integrity. However, to date, the toxicological profile of other Fusarium-derived metabolites, such as enniatins, beauvericin, moniliformin, apicidin, aurofusarin, rubrofusarin, equisetin and bikaverin, are poorly characterized. Thus we examined their effects—as metabolites alone and as metabolites in combination with DON—on the intestinal barrier function of differentiated intestinal porcine epithelial cells (IPEC-J2) over 72 h. Transepithelial electrical resistance (TEER) was measured at 24-h intervals, followed by evaluation of cell viability using neutral red (NR) assay. Enniatins A, A1, B and B1, apicidin, aurofusarin and beauvericin significantly reduced TEER. Moniliformin, equisetin, bikaverin and rubrofusarin had no effect on TEER. In the case of apicidin, aurofusarin and beauvericin, TEER reductions were further substantiated by the addition of otherwise no-effect DON concentrations. In all cases, viability was unaffected, confirming that TEER reductions were not due to compromised viability. Considering the prevalence of mycotoxin contamination and the diseases associated with intestinal barrier disruption, consumption of contaminated food or feed may have substantial health implications.

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“…To establish the in vitro model of the intestinal epithelial monolayer, Caco-2 cells were grown on commercial cell culture Transwell inserts (membrane area 0.33 cm 2 , pore size 0.4 mm; Corning, Corning, NY) for 21 days, during which time they undergo a process of spontaneous differentiation in culture and fully differentiate into mature enterocytes that simulate the intestinal epithelial cell barrier. 20 A stable measurement of transepithelial electrical resistance (TEER) over 3 days was used as an indicator of a wellestablished differentiated Caco-2 cell monolayer.…”

Section: Cell Culturementioning

confidence: 99%

Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability

Chen

Wang

Zhang

et al. 2017

The American Journal of Pathology

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Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. (Am J Pathol 2017, 187: 2686e2697; https://doi.

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Mycotoxins modify the barrier function of Caco-2 cells through differential gene expression of specific claudin isoforms: Protective effect of illite mineral clay

Cited by 91 publications

References 79 publications

Halloysite nanotubes as tools to improve the actual challenge of fixed doses combinations in tuberculosis treatment

Halloysite nanotubes as tools to improve the actual challenge of fixed doses combinations in tuberculosis treatment

Effect of Fusarium-Derived Metabolites on the Barrier Integrity of Differentiated Intestinal Porcine Epithelial Cells (IPEC-J2)

Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability

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