Dose and route dependent effects of the mycotoxin deoxynivalenol in a 3D gut-on-a-chip model with flow

Pöschl, Franziska; Höher, Theresa; Pirklbauer, Sarah; Wolinski, Heimo; Ressler, Miriam; Riederer, Monika; Lienhart, Lisa

doi:10.1016/j.tiv.2023.105563

Cited by 5 publications

(3 citation statements)

References 45 publications

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“…Very recently, DON-mediated effects on intestinal barrier leakage were further confirmed using a three-layered 3D gut-on-a-chip Caco-2 cell-culture model that allowed the inclusion of intestinal flow, ECM, and compartmentalization in three compartments (apical gut tube with lumen, ECM, and basolateral compartment). Similar to the previous findings, the intestinal cells were found to be more sensitive to basolateral DON exposure [ 141 ]. Noteworthy, with the addition of the third dimension and the application of fluid flow, shear stress, and the integration of the ECM, this study took one step further towards a more physiological model solution.…”

Section: Applications Of Advanced In Vitro Models For Mycotoxin Asses...supporting

confidence: 89%

The Growing Importance of Three-Dimensional Models and Microphysiological Systems in the Assessment of Mycotoxin Toxicity

Zingales

Esposito

Torriero

et al. 2023

Toxins

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Current investigations in the field of toxicology mostly rely on 2D cell cultures and animal models. Although well-accepted, the traditional 2D cell-culture approach has evident drawbacks and is distant from the in vivo microenvironment. To overcome these limitations, increasing efforts have been made in the development of alternative models that can better recapitulate the in vivo architecture of tissues and organs. Even though the use of 3D cultures is gaining popularity, there are still open questions on their robustness and standardization. In this review, we discuss the current spheroid culture and organ-on-a-chip techniques as well as the main conceptual and technical considerations for the correct establishment of such models. For each system, the toxicological functional assays are then discussed, highlighting their major advantages, disadvantages, and limitations. Finally, a focus on the applications of 3D cell culture for mycotoxin toxicity assessments is provided. Given the known difficulties in defining the safety ranges of exposure for regulatory agency policies, we are confident that the application of alternative methods may greatly improve the overall risk assessment.

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Section: Applications Of Advanced In Vitro Models For Mycotoxin Asses...supporting

confidence: 89%

The Growing Importance of Three-Dimensional Models and Microphysiological Systems in the Assessment of Mycotoxin Toxicity

Zingales

Esposito

Torriero

et al. 2023

Toxins

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show abstract

“…This difference in toxin sensitivity was also observed by Pöschl et al . when examining the effect on TEER after exposure of the Caco-2 OrganoPlate model to mycotoxin deoxynivalenol 31 . We could attribute this to an increased enterotoxin uptake by the Caco-2 cells cultured in the OrganoPlate which would explain why we did not find higher sensitivity of our model to melittin when compared to published data on Transwell 41 – 43 .…”

Section: Discussionmentioning

confidence: 99%

“…Further studies also showed how the platform can effectively mimic intestinal inflammatory disease conditions and can be used to assess intestinal drug permeability 29 , 30 . More recently, Pöschl et al reported the use of the platform to examine the effects of deoxynivalenol on barrier permeability, being the first to study enterotoxin toxicity using a high-throughput in vitro model with flow 31 . Together, these studies showcase the emerging potential of Caco-2 tubules as a model for toxicological assessment of enterotoxins.…”

Section: Introductionmentioning

confidence: 99%

A high-throughput gut-on-chip platform to study the epithelial responses to enterotoxins

Morelli,

Cabezuelo Rodríguez,

Queiroz

2024

Sci Rep

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Enterotoxins are a type of toxins that primarily affect the intestines. Understanding their harmful effects is essential for food safety and medical research. Current methods lack high-throughput, robust, and translatable models capable of characterizing toxin-specific epithelial damage. Pressing concerns regarding enterotoxin contamination of foods and emerging interest in clinical applications of enterotoxins emphasize the need for new platforms. Here, we demonstrate how Caco-2 tubules can be used to study the effect of enterotoxins on the human intestinal epithelium, reflecting toxins’ distinct pathogenic mechanisms. After exposure of the model to toxins nigericin, ochratoxin A, patulin and melittin, we observed dose-dependent reductions in barrier permeability as measured by TEER, which were detected with higher sensitivity than previous studies using conventional models. Combination of LDH release assays and DRAQ7 staining allowed comprehensive evaluation of toxin cytotoxicity, which was only observed after exposure to melittin and ochratoxin A. Furthermore, the study of actin cytoskeleton allowed to assess toxin-induced changes in cell morphology, which were only caused by nigericin. Altogether, our study highlights the potential of our Caco-2 tubular model in becoming a multi-parametric and high-throughput tool to bridge the gap between current enterotoxin research and translatable in vivo models of the human intestinal epithelium.

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Effective protective agents against organ toxicity of deoxynivalenol and their detoxification mechanisms: A review

Wang,

Yao,

Meng

et al. 2023

Food and Chemical Toxicology

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Dose and route dependent effects of the mycotoxin deoxynivalenol in a 3D gut-on-a-chip model with flow

Cited by 5 publications

References 45 publications

The Growing Importance of Three-Dimensional Models and Microphysiological Systems in the Assessment of Mycotoxin Toxicity

The Growing Importance of Three-Dimensional Models and Microphysiological Systems in the Assessment of Mycotoxin Toxicity

A high-throughput gut-on-chip platform to study the epithelial responses to enterotoxins

Effective protective agents against organ toxicity of deoxynivalenol and their detoxification mechanisms: A review

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