This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs) in mice. The lethal dose, 50 (LD50), of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg). The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the liver (10.24%ID/g), spleen (34.78%ID/g) and lung (1.96%ID/g). TEM imaging showed only a small amount in the hepatocytes of the liver and in the capillary endothelial cells of the lung and kidney. The levels of serum LDH, AST and ALT were all elevated in the SNP treated groups. A histological examination showed lymphocytic infiltration, granuloma formation, and hydropic degeneration in liver hepatocytes; megakaryocyte hyperplasia in the spleen; and pneumonemia and pulmonary interstitial thickening in the lung of the SNP treated groups. A CD68 immunohistochemistry stain indicated SNPs induced macrophage proliferation in the liver and spleen. The results suggest injuries induced by the SNPs in the liver, spleen and lungs. Mononuclear phagocytic cells played an important role in the injury process.
References
[1]
Yang X, Liu J, He H, Zhou L, Gong C, et al. (2010) SiO2 nanoparticles induce cytotoxicity and protein expression alteration in HaCaT cells. Part Fibre Toxicol 7: 1.
[2]
Chekman IS (2008) [Nanopharmacology: experimental and clinic aspect]. Lik Sprava 104–109.
[3]
Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH (2010) The nanosilica hazard: another variable entity. Part Fibre Toxicol 7: 39.
[4]
Shi Y, Yadav S, Wang F, Wang H (2010) Endotoxin promotes adverse effects of amorphous silica nanoparticles on lung epithelial cells in vitro. J Toxicol Environ Health A 73: 748–756.
[5]
Sohaebuddin SK, Thevenot PT, Baker D, Eaton JW, Tang L (2010) Nanomaterial cytotoxicity is composition, size, and cell type dependent. Part Fibre Toxicol 7: 22.
[6]
Li Y, Sun L, Jin M, Du Z, Liu X, et al. (2011) Size-dependent cytotoxicity of amorphous silica nanoparticles in human hepatoma HepG2 cells. Toxicol In Vitro 25: 1343–1352.
[7]
Chen M, von Mikecz A (2005) Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. Exp Cell Res 305: 51–62.
[8]
Eom HJ, Choi J (2009) Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas-2B. Toxicol In Vitro 23: 1326–1332.
[9]
Ye Y, Liu J, Xu J, Sun L, Chen M, et al. (2010) Nano-SiO2 induces apoptosis via activation of p53 and Bax mediated by oxidative stress in human hepatic cell line. Toxicol In Vitro 24: 751–758.
[10]
Nel A, Xia T, Madler L, Li N (2006) Toxic potential of materials at the nanolevel. Science 311: 622–627.
[11]
Sun L, Li Y, Liu X, Jin M, Zhang L, et al. (2011) Cytotoxicity and mitochondrial damage caused by silica nanoparticles. Toxicol In Vitro 25: 1619–1629.
[12]
Napierska D, Thomassen LC, Rabolli V, Lison D, Gonzalez L, et al. (2009) Size-dependent cytotoxicity of monodisperse silica nanoparticles in human endothelial cells. Small 5: 846–853.
[13]
Sayes CM, Reed KL, Glover KP, Swain KA, Ostraat ML, et al. (2010) Changing the dose metric for inhalation toxicity studies: short-term study in rats with engineered aerosolized amorphous silica nanoparticles. Inhal Toxicol 22: 348–354.
[14]
Cho WS, Choi M, Han BS, Cho M, Oh J, et al. (2007) Inflammatory mediators induced by intratracheal instillation of ultrafine amorphous silica particles. Toxicol Lett 175: 24–33.
[15]
Arts JH, Schijf MA, Kuper CF (2008) Preexposure to amorphous silica particles attenuates but also enhances allergic reactions in trimellitic anhydride-sensitized brown Norway rats. Inhal Toxicol 20: 935–948.
[16]
Xie G, Sun J, Zhong G, Shi L, Zhang D (2010) Biodistribution and toxicity of intravenously administered silica nanoparticles in mice. Arch Toxicol 84: 183–190.
[17]
Nishimori H, Kondoh M, Isoda K, Tsunoda S, Tsutsumi Y, et al. (2009) Histological analysis of 70-nm silica particles-induced chronic toxicity in mice. Eur J Pharm Biopharm 72: 626–629.
[18]
Cho M, Cho WS, Choi M, Kim SJ, Han BS, et al. (2009) The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles. Toxicol Lett 189: 177–183.
[19]
Liu T, Li L, Teng X, Huang X, Liu H, et al. (2011) Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice. Biomaterials 32: 1657–1668.
[20]
Dixon WJ (1965) The up-and-down method for small samples. J Am Stats Assoc 60: 967–978.
[21]
Hiller DB, Di Gregorio G, Kelly K, Ripper R, Edelman L, et al. (2010) Safety of high volume lipid emulsion infusion: a first approximation of LD50 in rats. Reg Anesth Pain Med 35: 140–144.
[22]
Nabeshi H, Yoshikawa T, Matsuyama K, Nakazato Y, Arimori A, et al. (2012) Amorphous nanosilicas induce consumptive coagulopathy after systemic exposure. Nanotechnology 23: 045101.
Park EJ, Park K (2009) Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro. Toxicol Lett 184: 18–25.
[25]
Liu T, Li L, Fu C, Liu H, Chen D, et al. (2012) Pathological mechanisms of liver injury caused by continuous intraperitoneal injection of silica nanoparticles. Biomaterials 33: 2399–2407.
[26]
Tseng MT, Lu X, Duan X, Hardas SS, Sultana R, et al. (2012) Alteration of hepatic structure and oxidative stress induced by intravenous nanoceria. Toxicol Appl Pharmacol 260: 173–182.
[27]
Osmond-McLeod MJ, Poland CA, Murphy F, Waddington L, Morris H, et al. (2011) Durability and inflammogenic impact of carbon nanotubes compared with asbestos fibres. Part Fibre Toxicol 8: 15.
[28]
Lam CW, James JT, McCluskey R, Hunter RL (2004) Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 77: 126–134.
[29]
Nishimori H, Kondoh M, Isoda K, Tsunoda S, Tsutsumi Y, et al. (2009) Silica nanoparticles as hepatotoxicants. Eur J Pharm Biopharm 72: 496–501.
[30]
Yarrington JT, Wallace CD, Loudy DE, Gibson JP (1992) Three-month effects of MDL 19,660 on the canine platelet and erythrocyte. Fundam Appl Toxicol 18: 247–254.
[31]
Koch CA, Li CY, Mesa RA, Tefferi A (2003) Nonhepatosplenic extramedullary hematopoiesis: associated diseases, pathology, clinical course, and treatment. Mayo Clin Proc 78: 1223–1233.
[32]
Iqbal MP, Mehboobali N, Haider G, Pervez S, Azam I (2012) Effects of betel nut on cardiovascular risk factors in a rat model. BMC Cardiovasc Disord 12: 94.
[33]
Gluhcheva Y, Atanasov V, Ivanova J, Mitewa M (2012) Cobalt-induced changes in the spleen of mice from different stages of development. J Toxicol Environ Health A 75: 1418–1422.
[34]
Kwon JT, Kim DS, Minai-Tehrani A, Hwang SK, Chang SH, et al. (2009) Inhaled fluorescent magnetic nanoparticles induced extramedullary hematopoiesis in the spleen of mice. J Occup Health 51: 423–431.
[35]
Cosgrove BD, Cheng C, Pritchard JR, Stolz DB, Lauffenburger DA, et al. (2008) An inducible autocrine cascade regulates rat hepatocyte proliferation and apoptosis responses to tumor necrosis factor-alpha. Hepatology 48: 276–288.
