Cupric Oxide Nanoparticles Induce Cellular Toxicity in Liver and Intestine Cell Lines.

Mahmoud Abudayyak,Elif Guzel,Gül Özhan

doi:10.34172/apb.2020.025

Mahmoud Abudayyak, Elif Guzel + Show 1 more

Open Access

https://doi.org/10.34172/apb.2020.025

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Abstract

Purpose: The wide application of cupric oxide nanoparticles (copper (II) oxide, CuO-NPs) in various fields has increased exposure to the kind of active nanomaterials, which can cause negative effects on human and environment health. Although CuO-NPs were reported to be harmful to human, there is still a lack information related to their toxic potentials. In the present study, the toxic potentials of CuO-NPs were evaluated in the liver (HepG2 hepatocarcinoma) and intestine (Caco-2 colorectal adenocarcinoma) cells. Methods: After the characterization of particles, cellular uptake and morphological changes were determined. The potential of cytotoxic, genotoxic, oxidative and apoptotic damage was investigated with several in vitro assays. Results: The average size of the nanoparticles was 34.9 nm, about 2%-5% of the exposure dose was detected in the cells and mainly accumulated in different organelles, causing oxidative stress, cell damages, and death. The IC50 values were 10.90 and 10.04 µg/mL by MTT assay, and 12.19 and 12.06 µg/mL by neutral red uptake (NRU) assay, in HepG2 and Caco-2 cells respectively. Apoptosis assumes to the main cell death pathway; the apoptosis percentages were 52.9% in HepG2 and 45.5% in Caco-2 cells. Comet assay result shows that the highest exposure concentration (20 µg/mL) causes tail intensities about 9.6 and 41.8%, in HepG2 and Caco-2 cells, respectively. Conclusion: CuO-NPs were found to cause significant cytotoxicity, genotoxicity, and oxidative and apoptotic effects in both cell lines. Indeed, CuO-NPs could be dangerous to human health even if their toxic mechanisms should be elucidated with further studies.

Highlights

People expose hazardously to nanoparticles – either anthropologically or as outputs of natural phenomena – via food, water, or air due to the gradual increases in nanomaterial usage in various aspects of life
Cu release into cell medium and cellular uptake The inductively coupled plasmamass spectrometry (ICP-MS) assay results show that Cu ions were not detected in cell-free medium, while 2%-5% of the exposure dose was detected in the cells, which indicates the uptake of CuO-NPs by HepG2 and Caco-2 cells following exposure for 24 h (Table 1)
The differences observed in cellular uptake could be due to the differences in the permeability

Summary

Introduction

People expose hazardously to nanoparticles – either anthropologically or as outputs of natural phenomena – via food, water, or air due to the gradual increases in nanomaterial usage in various aspects of life. Researches discourse that nanoparticles could be detected in the organs/tissues, brain, heart, liver etc.[1] copper (Cu)-based nanoparticles (NPs) were found in liver, kidney, and spleen following oral exposure.[2] CuO-NPs are widely used in gas sensors, catalysts, high-temperature conductors, solar energy converters, and antimicrobial agents in industry, cosmetics, and medicine owing to their high conductivity, electron correlation effects, and special physicochemical properties.[3,4] CuO-NPs caused morphological changes, necrosis, and dysfunction in liver, stomach, and kidney, disruption of the epithelial lining of the gastrointestinal tract and severe atrophy and color change in the spleen.[2,5,6,7,8,9] CuO-NPs caused acute death, abnormalities, and damage in embryo and gill of Zebrafish.[10] Generally, researchers have been interested in the toxic potentials of CuO-NPs on lung, skin, breast, brain and nervous system.[11,12,13,14,15] there are only a few reports on liver and intestine cells.[16,17,18,19] We comprehensively assessed the toxic potentials and toxicity mechanisms of CuO-NPs on HepG2 liver and Caco-2 intestinal cell lines Their cytotoxic, genotoxic, oxidative damage, and apoptosis-necrosis induction potentials were investigated in vitro conditions following NPs characterization and evaluation of their cellular uptake. Many researchers select these human cell lines as models of in vitro conditions to study the apical uptake, metabolism, and absorption of nutrients, chemicals and drugs.[20,21,22]

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