The size-dependent genotoxicity and oxidative stress of silica nanoparticles on endothelial cells
- 69 Downloads
Concerns over the health risk of the widely distributed, commonly used silica nanoparticles (SiNPs) are increasing worldwide. Yet, up to now, there are still many major knowledge gaps over the potential adverse effects of SiNP exposure on human cardiovascular health and the underlying mechanisms. In this study, comet assay and micronucleus test were employed to determine the genotoxic potentials of four sizes (10, 25, 50, 100 nm) of SiNPs to human umbilical vein endothelial cells (HUVECs) in culture. The intracellular redox statuses were explored through the determination of the levels of reactive oxygen species (ROS) and reduced glutathione (GSH) with kits, respectively. The protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were also detected by Western blot. The results showed that at the administrative levels (1, 5, 25 μg/mL), all the four sizes of SiNPs could induce an increase of both DNA damages and MN frequencies in HUVECs in culture, with a positive dose- and negative size-dependent effect relationship (S100 < S50 < S25 < S10). Also, significantly enhanced levels of intracellular ROS, but decreased levels of GSH, were observed in the SiNP-treated groups. Interestingly, a very similar manner of dose- and size-dependent effect relationship was observed between the ROS test and both comet assay and MN test, but contrary to that of GSH assay. Correspondingly, the levels of Nrf2 protein were also enhanced in the SiNP-treated HUVECs, with a negative size-dependent effect relationship. These results implicated that induction of oxidative stress and subsequent genotoxicity may be an important biological mechanism by which SiNP exposure may affect human cardiovascular health.
KeywordsSilica nanoparticle (SiNP) Endothelial cell (EC) Genotoxicity Oxidative stress
This paper was funded by the Science and Technology Foundation of Guangdong Province (2014B030301060) and the Foundation of University of South China, China (2012XQD44).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Davignon J, Ganz P (2004) Role of endothelial dysfunction in atherosclerosis. Circulation 109:III27–III32Google Scholar
- Jimenez-Villarreal J, Rivas-Armendariz DI, Arellano Perez-Vertti RD, Olivas Calderon E, Garcia-Garza R, Betancourt-Martinez ND, Serrano-Gallardo LB, Moran-Martinez J (2017) Relationship between lymphocyte DNA fragmentation and dose of iron oxide (Fe2O3) and silicon oxide (SiO2) nanoparticles. Genet Mol Res 16(1):1–12Google Scholar
- Keller AA, McFerran S, Lazareva A, Suh S (2013) Global life cycle releases of engineered nanomaterials. Journal of Nanoparticle Research 15(6): 1–17Google Scholar
- Kwon JY, Kim HL, Lee JY, Ju YH, Kim JS, Kang SH, Kim YR, Lee JK, Jeong J, Kim MK, Maeng EH, Seo YR (2014) Undetactable levels of genotoxicity of SiO2 nanoparticles in in vitro and in vivo tests. Int J Nanomedicine 9(Suppl 2):173–181Google Scholar
- Kyrtopoulos SA, Georgiadis P, Autrup H, Demopoulos N, Farmer P, Haugen A, Katsouyanni K, Lambert B, Ovrebo S, Sram R, Stefanou G, Topinka J (2001) Biomarkers of genotoxicity of urban air pollution overview and descriptive data from a molecular epidemiology study on populations exposed to moderate-to-low levels of polycyclic aromatic hydrocarbons: the AULIS project. Mutat Res 496:207–228CrossRefGoogle Scholar
- Nabeshi H, Yoshikawa T, Matsuyama K, Nakazato Y, Matsuo K, Arimori A, Isobe M, Tochigi S, Kondoh S, Hirai T, Akase T, Yamashita T, Yamashita K, Yoshida T, Nagano K, Abe Y, Yoshioka Y, Kamada H, Imazawa T, Itoh N, Nakagawa S, Mayumi T, Tsunoda SI, Tsutsumi Y (2011) Systemic distribution, nuclear entry and cytotoxicity of amorphous nanosilica following topical application. Biomaterials 32:2713–2724CrossRefGoogle Scholar
- Oostingh GJ, Casals E, Italiani P, Colognato R, Stritzinger R, Ponti J, Pfaller T, Kohl Y, Ooms D, Favilli F, Leppens H, Lucchesi D, Rossi F, Nelissen I, Thielecke H, Puntes VF, Duschl A, Boraschi D (2011) Problems and challenges in the development and validation of human cell-based assays to determine nanoparticle-induced immunomodulatory effects. Particle and Fibre Toxicol 8:8CrossRefGoogle Scholar
- Zhong Y, Feng SL, Luo Y, Zhang GD, Kong ZM (2001) Evaluating the genotoxicity of surface water of Yangzhong City using the Vicia faba micronucleus test and the comet assay. Bull Environ Contam Toxicol 67:217–224Google Scholar