Effect of Particle Size of Zinc Oxides on Cytotoxicity and Cell Permeability in Caco-2 Cells

Chang, Hyun-Joo; Choi, Sung‐Wook; Ko, Sanghoon; Chun, Hyang Sook

doi:10.3746/jfn.2011.16.2.174

Cited by 7 publications

(5 citation statements)

References 27 publications

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“…This finding is consistent with various in vivo and in vitro studies concerning HTs, tannic acid, and other polyphenolic compounds [20,49,50]. Conversely, existing literature on ZnO primarily focuses on nanoparticle formulations, which may induce increased cellular cytotoxicity [51]. However, zinc deficiency is linked to compromised selective intestinal permeability, observed in conditions like Crohn's disease and ulcerative colitis, marked by structural and functional alterations of ZO-1 and OCLN [52].…”

Section: Discussionsupporting

confidence: 84%

Combination of Hydrolysable Tannins and Zinc Oxide on Enterocyte Functionality: In Vitro Insights

Ciaramellano,

Scipioni,

Belà

et al. 2024

Preprint

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In the symptomatic treatment of gastrointestinal disorders, high dosages of zinc oxide (ZnO) were conventionally employed. However, concerns regarding the potential for microbial resistance and ecological detriment have arisen due to the excessive application of this compound. These concerns highlight the urgency to minimize the use of ZnO and to explore sustainable nutritional solutions. Hydrolysable tannins (HTs), known for their role in traditional medicine for acute gastrointestinal issues, emerge as a promising alternative. This study examined the combined effect of food-grade HTs and lower ZnO concentration on relevant biological functions of Caco-2 cells, a widely used model of the intestinal epithelial barrier. We found that, when used together, ZnO and HTs (ZnO/HTs) enhanced tissue repair and improved epithelial barrier function, normalizing the expression and functional organization of tight junction proteins. Finally, the ZnO/HTs combination strengthened enterocyte defence against oxidative stress induced by inflammation stimuli. In conclusion, combining ZnO and HTs may offer a suitable and practical approach for decreasing ZnO levels in veterinary medical applications.

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Section: Discussionsupporting

confidence: 84%

Combination of Hydrolysable Tannins and Zinc Oxide on Enterocyte Functionality: In Vitro Insights

Ciaramellano,

Scipioni,

Belà

et al. 2024

Preprint

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“…For example, translocation across the intestinal barrier and cytotoxic effects of a panel of zinc oxide (ZnO) NMs (of various sizes) has been studied using differentiated Caco-2 cells. It was observed that ZnO NMs (20 nm) had a higher level of permeation across the intestinal barrier and elicited greater cytotoxicity than larger particles (diameter of 1–5 μm or 90–200 nm) [ 60 ], demonstrating that particle translocation across the intestinal barrier may be a size dependent phenomenon. There is also evidence that gold NMs (1.4 to 200 nm) can translocate across the intestinal barrier of rats following ingestion [ 61 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of copper oxide nanomaterials on differentiated and undifferentiated Caco-2 intestinal epithelial cells; assessment of cytotoxicity, barrier integrity, cytokine production and nanomaterial penetration

et al. 2017

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BackgroundCopper oxide nanomaterials (CuO NMs) are exploited in a diverse array of products including antimicrobials, inks, cosmetics, textiles and food contact materials. There is therefore a need to assess the toxicity of CuO NMs to the gastrointestinal (GI) tract since exposure could occur via direct oral ingestion, mucocillary clearance (following inhalation) or hand to mouth contact.MethodsUndifferentiated Caco-2 intestinal cells were exposed to CuO NMs (10 nm) at concentrations ranging from 0.37 to 78.13 μg/cm2 Cu (equivalent to 1.95 to 250 μg/ml) and cell viability assessed 24 h post exposure using the alamar blue assay. The benchmark dose (BMD 20), determined using PROAST software, was identified as 4.44 μg/cm2 for CuO NMs, and 4.25 μg/cm2 for copper sulphate (CuSO4), which informed the selection of concentrations for further studies. The differentiation status of cells and the impact of CuO NMs and CuSO4 on the integrity of the differentiated Caco-2 cell monolayer were assessed by measurement of trans-epithelial electrical resistance (TEER), staining for Zonula occludens-1 (ZO-1) and imaging of cell morphology using scanning electron microscopy (SEM). The impact of CuO NMs and CuSO4 on the viability of differentiated cells was performed via assessment of cell number (DAPI staining), and visualisation of cell morphology (light microscopy). Interleukin-8 (IL-8) production by undifferentiated and differentiated Caco-2 cells following exposure to CuO NMs and CuSO4 was determined using an ELISA. The copper concentration in the cell lysate, apical and basolateral compartments were measured with Inductive Coupled Plasma Optical Emission Spectrometry (ICP-OES) and used to calculate the apparent permeability coefficient (Papp); a measure of barrier permeability to CuO NMs. For all experiments, CuSO4 was used as an ionic control.ResultsCuO NMs and CuSO4 caused a concentration dependent decrease in cell viability in undifferentiated cells. CuO NMs and CuSO4 translocated across the differentiated Caco-2 cell monolayer. CuO NM mediated IL-8 production was over 2-fold higher in undifferentiated cells. A reduction in cell viability in differentiated cells was not responsible for the lower level of cytokine production observed. Both CuO NMs and CuSO4 decreased TEER values to a similar extent, and caused tight junction dysfunction (ZO-1 staining), suggesting that barrier integrity was disrupted.ConclusionsCuO NMs and CuSO4 stimulated IL-8 production by Caco-2 cells, decreased barrier integrity and thereby increased the Papp and translocation of Cu. There was no significant enhancement in potency of the CuO NMs compared to CuSO4. Differentiated Caco-2 cells were identified as a powerful model to assess the impacts of ingested NMs on the GI tract.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-017-0211-7) contains supplementary material, which is available to authorized users.

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“…This finding is consistent with various in vivo and in vitro studies concerning HTs, tannic acid, and other polyphenolic compounds [ 20 , 51 , 52 ]. Conversely, the existing literature on ZnO primarily focuses on nanoparticle formulations, which may induce increased cellular cytotoxicity [ 53 ]. However, zinc deficiency is linked to compromised selective intestinal permeability, which is observed in conditions like Crohn’s disease and ulcerative colitis, marked by structural and functional alterations of ZO-1 and OCLN [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Combination of Hydrolysable Tannins and Zinc Oxide on Enterocyte Functionality: In Vitro Insights

Ciaramellano,

Scipioni,

Belà

et al. 2024

Biomolecules

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The management of gastrointestinal disease in animals represents a significant challenge in veterinary and zootechnic practice. Traditionally, acute symptoms have been treated with antibiotics and high doses of zinc oxide (ZnO). However, concerns have been raised regarding the potential for microbial resistance and ecological detriment due to the excessive application of this compound. These concerns highlight the urgency of minimizing the use of ZnO and exploring sustainable nutritional solutions. Hydrolysable tannins (HTs), which are known for their role in traditional medicine for acute gastrointestinal issues, have emerged as a promising alternative. This study examined the combined effect of food-grade HTs and subtherapeutic ZnO concentration on relevant biological functions of Caco-2 cells, a widely used model of the intestinal epithelial barrier. We found that, when used together, ZnO and HTs (ZnO/HTs) enhanced tissue repair and improved epithelial barrier function, normalizing the expression and functional organization of tight junction proteins. Finally, the ZnO/HTs combination strengthened enterocytes’ defense against oxidative stress induced by inflammation stimuli. In conclusion, combining ZnO and HTs may offer a suitable and practical approach for decreasing ZnO levels in veterinary nutritional applications.

show abstract

Effect of Particle Size of Zinc Oxides on Cytotoxicity and Cell Permeability in Caco-2 Cells

Cited by 7 publications

References 27 publications

Combination of Hydrolysable Tannins and Zinc Oxide on Enterocyte Functionality: In Vitro Insights

Combination of Hydrolysable Tannins and Zinc Oxide on Enterocyte Functionality: In Vitro Insights

Impact of copper oxide nanomaterials on differentiated and undifferentiated Caco-2 intestinal epithelial cells; assessment of cytotoxicity, barrier integrity, cytokine production and nanomaterial penetration

Combination of Hydrolysable Tannins and Zinc Oxide on Enterocyte Functionality: In Vitro Insights

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