Silver Nanoparticles Induced Immunotoxicity-Based Early Systemic Toxicity
Abstract: Objective: To investigate the effects on immune system and other systemic toxicity of silver nano-particles (SNPs) in rats by oral exposure, and combined an in vitro study of SNPs on the release of inflammatory cytokines and immune factors in lymphocytes, to get a better understanding about potential immunotoxicity of silver nanoparticles. Methods: SD rats were orally administrated with low-dose (1 mg/kg) and high-dose (10 mg/kg) of SNPs and saline (control) respectively, and the organ and blood samples were harvested after 2 hrs (n = 9), 7 days (n = 18), 14 days (n = 18) ex-posure and14 days of post-exposure (n = 9) for determination of silver content, hematology, blood biochemistry, and immune factor assessment. Lymphocytes were incubated with or without lipo-polysaccharide in the presence or absence of silver nanoparticles for 24 hours in vitro. And IL-6, IL-4, IgG and IgE of cell culture supernatants were analyzed by ELISA. Results and Discussion: SNPs exposure group showed SNPs accumulated time-dose dependently in blood and organs of rats. The IgG (14 days), IgE (14 days) and IL-4 (7 days) of rats after 10 mg/kg SNPs exposure were signifi-cantly increased, and IL-6 and CD45RA+ (B cells) at 14 days post-exposure of SNPs were obviously increased, compared with that in control. But we did not find significant pathological changes. The rise of glucose and ALP suggested damage of pancreas and liver of rats after SNPs oral administra-tion. Low concentration silver in blood increased inflammatory cells in response to the stimuli by blood examination, while high concentration induced cytotoxicity which inhibited the normal growth of lymphocyte. Secretion of IgG and IL-6 induced by LPS of lymphocytes in low-dose and high-dose (0.5 μg/ml, 5 μg/ml) SNPs exposure was inhibited in vitro. In conclusion, our study showed that silver nanoparticles mainly caused a Th2-type immune toxicity-based early systemic toxicity.
文章引用: 邵安良 , 王志杰 , 陈 亮 , 徐丽明 (2014) 纳米银诱导的以免疫毒性为主的早期全身毒性研究。 免疫学研究， 2， 33-47. doi: 10.12677/IS.2014.24006
 Xu, L., Shi, C., Shao, A., et al. (2014) Toxic responses in rat embryonic cells to silver nanoparticles and released silver ions as analyzed via gene expression profiles and transmission electron microscopy. Nanotoxicology, 1-10.
 Xu, L., Shao, A., Zhao, Y., et al. (2014) Neurotoxicity of silver nanoparticles in rat brain after intragastric exposure. Journal of Nanoscience and Nanotechnology, 14, 1-9.
 Bouwmeester, H., Poortman, J., Peters, R.J., et al. (2011) Characteri-zation of translocation of silver nanoparticles and effects on whole-genome gene expression using an in vitro intestinal epithelium coculture model. ACS Nano, 5, 4091- 5103.
 Shavandi, Z., Ghazanfari, T. and Moghaddam, K.N. (2011) In vitro toxicity of silver nanoparticles on murine peritoneal macrophages. Immunopharmacology Immunotoxicology, 33, 135-140.
 Beer, C., Foldbjerg, R., Hayashi, Y., et al. (2012) Toxicity of silver nanoparticles—Nanoparticle or silver ion? Toxicology Letters, 208, 286-292.
 Mukherjee, S.G., O’Claonadh, N., Casey, A., et al. (2012) Comparative in vitro cytotoxicity study of silver nanoparticle on two mammalian cell lines. Toxicology in Vitro, 26, 238-251.
 El Badawy, A.M., Silva, R.G., Morris, B., et al. (2011) Surface charge-dependent toxicity of silver nanoparticles. En-vironmental Science Technology, 45, 283-287.
 Schäfer, B., Tentschert, J. and Luch, A. (2011) Nanosilver in consumer products and human health: More information required! Environmental Science Technology, 45, 7589-7590.
 Ahamed, M., Alsalhi, M.S. and Siddiqui, M.K. (2010) Silver nanoparticle applications and human health. Clinica Chimica Acta, 411, 1841-1848.
 Johnston, H.J., Hutchison, G., Christensen, F.M., et al. (2011) A review of the in vivo and in vitro toxicity of silver and gold particulates: Particle attributes and biological mechanisms responsible for the observed toxicity. Critical Reviews in Toxicology, 40, 328-346.
 Sung, J.H., Ji, J.H., Song, K.S., Lee, J.H., Choi, K.H., Lee, S.H. and Yu, I.J. (2011) Acute inhalation toxicity of silver nanoparticles. Toxicology and Industrial Health, 27, 149-154.
 Sung, J.H., Ji, J.H., Park, J.D., Song, M.Y., Song, K.S., Ryu, H.R., et al. (2011) Subchronic inhalation toxicity of gold nanoparticles. Particle and Fibre Toxicology, 8, 1-16.
 Stebounova, L.V., Adamcakova-Dodd, A., Kim, J.S., Park, H., O’Shaughnessy, P.T., Grassian, V.H. and Thorne, P.S. (2011) Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model. Particle and Fibre Toxicology, 8, 1-5.
 Korani, M., Rezayat, S.M., Gilani, K., Arbabi Bidgoli, S. and Adeli, S. (2011) Acute and subchronic dermal toxicity of nanosilver in guinea pig. International Journal of Nanomedicine, 6, 855-862.
 Kim, Y.S., Song, M.Y., Park, J.D., Song, K.S., Ryu, H.R., Chung, Y.H., et al. (2010) Subchronic oral toxicity of silver nanoparticles. Particle and Fibre Toxicology, 7, 1-20.
 Sung, J.H., Ji, J.H., Park, J.D., Yoon, J.U., Kim, D.S., Jeon, K.S., et al. (2009) Subchronic inhalation toxicity of silver nanoparticles. Toxicolology Science, 108, 452-461.
 Sung, J.H., Ji, J.H., Yoon, J.U., Kim, D.S., Song, M.Y., Jeong, J., et al. (2008) Lung function changes in Sprague-Dawley rats after prolonged inhalation exposure to silver nanoparticles. Inhalation Toxicology, 20, 567-574.
 Ji, J.U., Jung, J.H., Kim, S.S., Yoon, J.U., Park, J.D., Choi, B.S., et al. (2007) Twenty-eight-day inhalation toxicity study of silver nanoparticles in Sprague-Dawley rats. Inhalation Toxicology, 19, 857-871.
 Tang, J., Xiong, L., Wang, S., Wang, J., Liu, L., Li, J., et al. (2009) Distribution, translocation and accumulation of silver nanoparticles in rats. Journal of Nanoscience and Nanotechnology, 9, 4924-4932.
 Fadel, T.R., Look, M., Staffier, P.A., Haller, G.L., Pfefferle, L.D., Fahmy, T.M., et al. (2010) Clustering of stimuli on single-walled carbon nanotube bundles enhances cellular activation. Langmuir, 26, 5645-5654.
 Chrastina, A. and Schnitzer, J.E. (2010) Iodine-125 radiolabeling of silver nanoaprticles for in vivo SPECT imaging. International Journal of Nanomedicine, 5, 653-659.
 Meng, J., Yang, M., Jia, F., Xu, Z., Kong, H., Xu, H., et al. (2011) Immune responses of BALB/c mice to subcutaneously injected multi-walled carbon nanotubes. Nanotoxicology, 5, 583-591.
 Meng, J., Yang, M., Jia, F., Kong, H., Zhang, W., Wang, C., et al. (2010) Subcutaneous injection of water-soluble multi-walled carbon nanotubes in tumor-bearing mice boosts the host immune activity. Nanotechnology, 21, Article ID: 145104.
 刘焕亮, 杨丹凤, 张华山, 杨红莲, 张伟, 刘丽华, 等 (2010) 3种典型纳米材料致大鼠免疫毒性的作用. 解放军预防医学杂志, 3, 163-166.
 Park, E.J., Bae, E., Yi, J., Kim, Y., Choi, K., Lee, S.H., et al. (2010) Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nanoparticle. Environmental Toxicology and Pharmacology, 30, 162- 168.
 Hackenberg, S., Scherzed, A., Kessler, M., Hummel, S., Technau, A., Froelich, K., et al. (2011) Silver nanoparticles: Evaluation of DNA damage, toxicity and functional impairment in human mesenchymal stem cells. Toxicology Letters, 201, 27-33.
 Xu, L.M., Takemura, T., Xu, M.S., Hanagata, N. (2011) Toxicity of silver nanoparticles as assessed by global gene expression analysis. Materials Express, 1, 74-79.
 Xu, L., Li, X., Takemura, T., Hanagata, N., Wu, G. and Chou, L.L. (2012) Genotoxicity and molecular response of silver nanoparticle (NP)-based hydrogel. Journal of Nanobiotechnology, 10, 16.
 Li, X., Xu, L., Shao, A., Wu, G. and Hanagata, N. (2013) Cytotoxic and genotoxic effects of silver nanoparticles on primary Syrian hamster embryo (SHE) cells. Journal of Nanoscience and Nanotechnology, 13, 161-170.
 Park, M.V., Neigh, A.M., Vermeulen, J.P., de la Fonteyne, L.J., Verharen, H.W., Briedé, J.J., et al. (2011) The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles. Biomaterials, 32, 9810-9817.
 Carlson, C., Hussain, S.M., Schrand, A.M., Braydich-Stolle, L.K., Hess, K.L., Jones, R.L. and Schlager, J.J. (2008) Unique cellular interaction of silver nanoparticles: Size-dependent generation of reactive oxygen species. The Journal of Physical Chemistry B, 112, 13608-13619.
 Liu, W., Wu, Y., Wang, C., Li, H.C., Wang, T., Liao, C.Y., et al. (2010) Impact of silver nanoparticles on human cells: Effect of particle size. Nanotoxicology, 4, 319-330.
 De Jong, W.H. and Borm, P.J. (2008) Drug delivery and nanoparticles: Applications and hazards. International Journal of Nanomedicine, 3, 133-149.
 Kim, J.H., Kim, C.S., Ignacio, R.M., Kim, D.H., Sajo, M.E., Maeng, E.H., et al. (2014) Immunotoxicity of silicon dioxide nanoparticles with different sizes and electrostatic charge. International Journal of Nanomedicine, 9, 183-193.
 Hong, J., Wang, L., Zhao, X., Yu, X., Sheng, L., Xu, B., et al. (2014) Th2 factors may be involved in TiO2 NP-induced hepatic inflammation. Journal of Agricultural and Food Chemistry, 62, 6871-6878.