Abstract
Non-alcoholic fatty liver disease (NAFLD), mainly characterized by the accumulation of excess fat in hepatocytes, is the most prevalent liver disorder afflicting ~25% of adults worldwide. In vivo studies have shown that adult rodents with NAFLD were more sensitive to metallic nanoparticles (MNPs) than healthy MNPs. However, due to the complex interactions between various cell types in a fatty liver, it has become a major challenge to reveal the toxic effects of MNPs to specific types of liver cells such as steatotic hepatocytes. In this study, we reported the susceptibility of steatotic hepatocytes in cytotoxicity and the induction of oxidative stress to direct exposures to MNPs with different components (silver, ZrO2, and TiO2 NPs) and sizes (20–30 nm and 125 nm) in an oleic acid (OA) -induced steatotic HepG2 (sHepG2) cell model. Furthermore, the inhibitory potential of MNPs against the process of fatty acid oxidation (FAO) were obvious in sHepG2 cells, even at extremely low doses of 2 or 4 μg/mL, which was not observed in non-steatotic HepG2 (nHepG2) cells. Further experiments on the differential cell uptake of MNPs in nHepG2 and sHepG2 cells demonstrated that the susceptibility of steatotic hepatocytes to MNP exposures was in association with the higher cellular accumulation of MNPs. Overall, our study demonstrated that it is necessary and urgent to take the intracellular exposure dose into consideration when assessing the potential toxicity of environmentally exposed MNPs.
Highlights
The widespread applications of nanomaterials in various areas such as consumer products [1], agriculture [2], biomedicine [3] and environmental remediation [4] result in their higher environmental release and human exposure
All four Metallic nanoparticles (MNPs) selected were spherical in shape, with transmission electron microscope (TEM) sizes of 23.58 ± 6.30, 28.15 ± 6.31, 21.16 ± 5.04, and 125.28 ± 41.16 nm for Ag NPs, ZrO2 NPs, small-sized TiO2 NPs, and large-sized TiO2 NPs, respectively (Figure 1)
The hydrodynamic diameters of these NPs were generally much larger than their TEM sizes, which were further enlarged in minimum essential medium (MEM) cell culture medium supplemented with 10% fetal bovine serum (FBS) due to the adsorption of proteins on the surface (Figure 1E)
Summary
The widespread applications of nanomaterials in various areas such as consumer products [1], agriculture [2], biomedicine [3] and environmental remediation [4] result in their higher environmental release and human exposure. Metallic nanoparticles (MNPs) are among the largest classes of engineered nanoparticles (NPs) found in daily life. Commercial products containing MNPs account for 70% of the listed entries with identified NPs supplemented [5]. Exposed MNPs may enter the human body, interact with biomolecules, and perturb various physiological systems [6,7]. Such adverse outcomes in response to MNP exposure may be further aggravated in susceptible populations characterized by underdeveloped protection mechanisms, impaired self-repair ability, and/or compromised immunity [8,9,10]. It is urgent to reveal the potential toxic effects of engineered MNPs to various susceptible populations
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