Cellular Uptake and Toxicological Effects of Differently Sized Zinc Oxide Nanoparticles in Intestinal Cells

Mittag, Anna; Hoera, Christian; Kämpfe, Alexander; Westermann, Martin; Kuckelkorn, Jochen; Schneider, Thomas; Glei, Michael

doi:10.3390/toxics9050096

Cited by 27 publications

(17 citation statements)

References 66 publications

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“…The smaller nanoparticles (e.g., ZnO_Intra; about 16.7 nm) have an extraordinary ability to internalize into living cells through different biological mechanisms and reach the nucleus, thereby generating genotoxic damage with the consequent triggering of apoptosis. Mittag et al [74] investigated the cellular uptake of two differently sized ZnO NPs (<50 nm and <100 nm) against two human intestinal cell lines (Caco-2 and LT97). The outcomes of this study showed that ZnO NPs, at smaller sizes (<50 nm), led to the formation of micronuclei in LT97 cells.…”

Section: Cytotoxicity Of Zno Npsmentioning

confidence: 99%

Comparison Study of Cytotoxicity of Bare and Functionalized Zinc Oxide Nanoparticles

Król‐Górniak

Rafińska

Monedeiro

et al. 2021

IJMS

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In this paper, a study of the cytotoxicity of bare and functionalized zinc oxide nanoparticles (ZnO NPs) is presented. The functionalized ZnO NPs were obtained by various types of biological methods including microbiological (intra- and extracellular with Lactobacillus paracasei strain), phytochemical (Medicago sativa plant extract) and biochemical (ovalbumin from egg white protein) synthesis. As a control, the bare ZnO NPs gained by chemical synthesis (commercially available) were tested. The cytotoxicity was measured through the use of (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye as well as lactate dehydrogenase (LDH) assays against murine fibroblast L929 and Caco-2 cell lines. As a complementary method, scanning electron microscopy (SEM) was performed to assess the morphology of the tested cells after treatment with ZnO NPs. The microscopic data confirmed the occurrence of apoptotic blebbing and loss of membrane permeability after the administration of all ZnO NPs. The reactive oxygen species (ROS) concentration during the cell lines’ exposure to ZnO NPs was measured fluorometrically. Additionally, the photocatalytic degradation of methylene blue (MB) dye in the different light conditions, as well as the antioxidant activity of bare and functionalized ZnO NPs, is also reported. The addition of all types of tested ZnO NPs to methylene blue resulted in enhanced rates of photo-degradation in the presence of both types of irradiation, but the application of UV light resulted in higher photocatalytic activity of ZnO NPs. Furthermore, bare (chemically synthetized) NPs have been recognized as the strongest photocatalysts. In the context of the obtained results, a mechanism underlying the toxicity of bio-ZnO NPs, including (a) the generation of reactive oxygen species and (b) the induction of apoptosis, is proposed.

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Section: Cytotoxicity Of Zno Npsmentioning

confidence: 99%

Comparison Study of Cytotoxicity of Bare and Functionalized Zinc Oxide Nanoparticles

Król‐Górniak

Rafińska

Monedeiro

et al. 2021

IJMS

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“…There were only minor differences between ZnO NP and ZnCl 2 regarding the proportions of free zinc ions and bonded zinc. Digested ZnO NP showed no structural similarities with the pristine large, rod-shaped particles, which we have already characterized [ 28 ].…”

Section: Discussionmentioning

confidence: 91%

Impact of in vitro digested zinc oxide nanoparticles on intestinal model systems

et al. 2022

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Background Zinc oxide nanoparticles (ZnO NP) offer beneficial properties for many applications, especially in the food sector. Consequently, as part of the human food chain, they are taken up orally. The toxicological evaluation of orally ingested ZnO NP is still controversial. In addition, their physicochemical properties can change during digestion, which leads to an altered biological behaviour. Therefore, the aim of our study was to investigate the fate of two different sized ZnO NP (< 50 nm and < 100 nm) during in vitro digestion and their effects on model systems of the intestinal barrier. Differentiated Caco-2 cells were used in mono- and coculture with mucus-producing HT29-MTX cells. The cellular uptake, the impact on the monolayer barrier integrity and cytotoxic effects were investigated after 24 h exposure to 123–614 µM ZnO NP. Results In vitro digested ZnO NP went through a morphological and chemical transformation with about 70% free zinc ions after the intestinal phase. The cellular zinc content increased dose-dependently up to threefold in the monoculture and fourfold in the coculture after treatment with digested ZnO NP. This led to reactive oxygen species but showed no impact on cellular organelles, the metabolic activity, and the mitochondrial membrane potential. Only very small amounts of zinc (< 0.7%) reached the basolateral area, which is due to the unmodified transepithelial electrical resistance, permeability, and cytoskeletal morphology. Conclusions Our results reveal that digested and, therefore, modified ZnO NP interact with cells of an intact intestinal barrier. But this is not associated with serious cell damage.

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“…It was speculated, however, that pony-sized ZnO NPs were more toxic than large particles, merely at low concentrations, whereas they may present an equal level of risk at high concentrations, possibly due to the tendency of pony-sized nanomaterials to agglomerate [ 56 ]. In addition to cell viability indicators, the teratogenic potential was also mainly reflected in the ZnO NPs with a small diameter, which could lead to the emergence of a micronucleus in the LT97 cell at 50 nm, not at 100 nm [ 57 ]. As is consistent with these comparative tests, here, the RNA sequencing clarified that compared with ordinary ZnO, ZnO NPs demonstrated stronger lethality to hepatocytes, brought more severe inhibition of cell detoxification and caused more interference with antioxidation processes and membrane function ( Figure 4 , Figure 5 and Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

Lethality of Zinc Oxide Nanoparticles Surpasses Conventional Zinc Oxide via Oxidative Stress, Mitochondrial Damage and Calcium Overload: A Comparative Hepatotoxicity Study

Pei

Jiang

et al. 2022

IJMS

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Zinc oxide nanoparticles (ZnO NPs) with high bioavailability and excellent physicochemical properties are gradually becoming commonplace as a substitute for conventional ZnO materials. The present study aimed to investigate the hepatotoxicity mechanism of ZnO NPs and traditional non-nano ZnO particles, both in vivo and in vitro, and identify the differences in their toxic effects. The results showed that the extent and conditions of zinc ion release from ZnO NPs were inconsistent with those of ZnO. The RNA-seq results revealed that the expression quantity of differentially expressed genes (DEGs) and differentially expressed transcripts (DETs) affected by ZnO NPs was more than in ZnO, and the overall differences in genes or transcripts in the ZnO NPs group were more pronounced than in the ZnO group. Furthermore, the cell inactivation, oxidative stress, mitochondrial damage, and intracellular calcium overload induced by ZnO NPs were more serious than ZnO in HepG2 cells. Moreover, compared with traditional ZnO, the rat liver damage induced by ZnO NPs was more significant, with evidence of higher AST and ALT levels, weaker antioxidant capacity, and more serious histopathological damage (p < 0.05). In summary, the hepatotoxicity of ZnO NPs was more serious than that of conventional ZnO, which is helpful to understand the hepatotoxicity mechanism of Zn compounds in different states and improve the risk assessment of novel nano ZnO products in a variety of applications.

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Cellular Uptake and Toxicological Effects of Differently Sized Zinc Oxide Nanoparticles in Intestinal Cells

Cited by 27 publications

References 66 publications

Comparison Study of Cytotoxicity of Bare and Functionalized Zinc Oxide Nanoparticles

Comparison Study of Cytotoxicity of Bare and Functionalized Zinc Oxide Nanoparticles

Impact of in vitro digested zinc oxide nanoparticles on intestinal model systems

Lethality of Zinc Oxide Nanoparticles Surpasses Conventional Zinc Oxide via Oxidative Stress, Mitochondrial Damage and Calcium Overload: A Comparative Hepatotoxicity Study

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