Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles
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) th...
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12643 |
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| author | Xiaoli Zhang Yongyi Wei Chengjun Li Weiyu Wang Rui Zhang Jianbo Jia Bing Yan |
| author_facet | Xiaoli Zhang Yongyi Wei Chengjun Li Weiyu Wang Rui Zhang Jianbo Jia Bing Yan |
| author_sort | Xiaoli Zhang |
| collection | DOAJ |
| description | 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, ZrO<sub>2</sub>, and TiO<sub>2</sub> 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. |
| first_indexed | 2024-03-10T04:53:43Z |
| format | Article |
| id | doaj.art-d70431593f13418286dea154351e9246 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:53:43Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d70431593f13418286dea154351e92462023-11-23T02:25:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231264310.3390/ijms222312643Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic NanoparticlesXiaoli Zhang0Yongyi Wei1Chengjun Li2Weiyu Wang3Rui Zhang4Jianbo Jia5Bing Yan6Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Institute of Environmental Research at Greater Bay Area, Guangzhou University, Guangzhou 510006, ChinaSchool of Environmental Science and Engineering, Shandong University, Qingdao 266237, ChinaKey Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Institute of Environmental Research at Greater Bay Area, Guangzhou University, Guangzhou 510006, ChinaKey Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Institute of Environmental Research at Greater Bay Area, Guangzhou University, Guangzhou 510006, ChinaKey Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Institute of Environmental Research at Greater Bay Area, Guangzhou University, Guangzhou 510006, ChinaKey Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Institute of Environmental Research at Greater Bay Area, Guangzhou University, Guangzhou 510006, ChinaKey Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Institute of Environmental Research at Greater Bay Area, Guangzhou University, Guangzhou 510006, ChinaNon-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, ZrO<sub>2</sub>, and TiO<sub>2</sub> 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.https://www.mdpi.com/1422-0067/22/23/12643susceptible populationnanotoxicitysteatotic hepatocyteslipid metabolismintracellular exposure dose |
| spellingShingle | Xiaoli Zhang Yongyi Wei Chengjun Li Weiyu Wang Rui Zhang Jianbo Jia Bing Yan Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles International Journal of Molecular Sciences susceptible population nanotoxicity steatotic hepatocytes lipid metabolism intracellular exposure dose |
| title | Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles |
| title_full | Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles |
| title_fullStr | Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles |
| title_full_unstemmed | Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles |
| title_short | Intracellular Exposure Dose-Associated Susceptibility of Steatotic Hepatocytes to Metallic Nanoparticles |
| title_sort | intracellular exposure dose associated susceptibility of steatotic hepatocytes to metallic nanoparticles |
| topic | susceptible population nanotoxicity steatotic hepatocytes lipid metabolism intracellular exposure dose |
| url | https://www.mdpi.com/1422-0067/22/23/12643 |
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