Abstract
Due to the intensive commercial application of silver nanoparticles (Ag-NPs), their health risk assessment is of great importance. For acute toxicity evaluation of orally administered Ag-NPs, induction of reactive oxygen species (ROS), activity of liver function enzymes [(alanine (ALT/GPT), aspartate (AST/GOT), alkaline phosphatase (ALP)], concentration of lipid hydroperoxide (LHP), comet assay, and histopathology of liver in the rat model were performed. Four groups of five male rats were orally administered Ag-NPs, once a day for five days with doses of 5, 25, 50, 100 mg/kg, body weight. A control group was also made of five rats. Blood and liver were collected 24 h after the last treatment following standard protocols. Ag-NPs exposure increased the induction of ROS, activities of the liver enzymes (ALT, AST, ALP), concentration of lipid hydroperoxide (LHP), tail migration, and morphological alterations of the liver tissue in exposed groups compared to control. The highest two doses, 50 and 100 mg/kg showed statistically significant (p < 0.05) increases in ROS induction, ALT, AST, ALP activity, LHP concentration, DNA damage, and morphological alterations of liver compared to control. Based on these results, it is suggested that short-term administration of high doses of Ag-NP may cause organ toxicity and oxidative stress.
Similar content being viewed by others
References
Lee YH, Cheng FY, Chiu HW, Tsai JC, Fang CY, Chen CW, Wang YJ (2014) Cytotoxicity, oxidative stress, apoptosis and the autophagic effects of silver nanoparticles in mouse embryonic fibroblasts. Biomaterials 35(16):4706–4715
Chen X, Schluesener HJ (2008) Nanosilver a product in medical application. Toxicol Lett 176:1–12
Tripathy A, Chandrasekran N, Raichur AM, Mukherjee A (2008) Antibacterial applications of silver nanoparticles synthesized by aqueous extract of Azadirachta indica (Neem) leaves. J Biomed Nanotech 4:1–6
Kim HR, Kim MJ, Lee SY, Oh SM, Chung KH (2011) Genotoxic effects of silver nanoparticles stimulated by oxidative stress in human normal bronchial epithelial (BEAS-2B) cells. Mutat Res 726(2):129–135
Stebounova LV, Adamcakova-Dodd A, Kim JS, Park H, O’Shaughnessy PT, Grassain VH, and Thorne PS (2011) Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model. Part and FibreToxicol. 8.5
Tiwari DK, Jin T, Behari J (2011) Dose-dependent in vivo toxicity assessment of silver nanoparticle in Wistar rats. Toxicol Mech Methods 21(1):13–24
Gliga AR, Skoglund S, Wallinder IO, Fadeel B, Karlsson HL (2014) Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release. Part Fibre Toxicol 11:11
Lee TY, Liu MS, Huang LJ, Lue SI, Lin LC, Kwan AL, Yang RC (2013) Bioenergetic failure correlates with autophagy and apoptosis in rat liver following silver nanoparticle intraperitoneally administration. Part Fibre Toxicol 10(1):40
Xue Y, Zhang S, Huang Y, Zhang T, Liu X, Hu Y, Zhang Z, Tang M (2012) Acute toxic effects and gender-related biokinetics of silver nanoparticles following an intravenous injection in mice. J Appl Toxicol 32:890–899
Kim YS, Kim JS, Cho HS, Rha DS, Park JD, Choi BS, Lim R, Chang HK, Chung YH, Kwon IH, Jeong J, Han BS, Yu IJ (2008) Twenty-eight day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats. Inhal Toxicol 20:575–583
AshaRani PV, Mun GLK, Hande MP, Valiyaveettil S (2009) Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACSNano 3:279–290
Rahman MF, Wang J, Patterson TA, Saini UT, Robinson BL, Newport GD, Murdock RC, Schlager JJ, Hussain SM, Ali SF (2009) Expression of genes related to oxidative stress in mouse brain after exposure to silver-25 nanoparticles. Toxicol Lett 187:15–21
Shi J, Sun X, Lin Y, Zou X, Li Z, Liao Y, Du M, Zhang H (2014) Endothelial cell injury and dysfunction induced by silver nanoparticles through oxidative stress via IKK/NF-κB pathways. Biomaterials S0142-9612(14)00491-8
Gaiser BK, Hirn S, Kermanizadeh A, Kanase N, Fytianos K, Wenk A, Haberl N, Brunelli A, Kreyling WG, Stone V (2013) Effects of silver nanoparticles on the liver and hepatocytes in vitro. Toxicol Sci 131(2):537–547
Mukherjee SG, O’Claonadh N, Casey A, Chambers G (2012) Comparative in vitro cytotoxicity study of silver nanoparticle on two mammalian cell lines. Toxicol In Vitro 26(2):238–251
Kawata K, Osawa M, Okabe S (2009) In vitro toxicity of silver nanoparticles at noncytotoxic doses to HepG2 human hepatoma cells. Environ Sci Technol 43:6046–6051
Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ (2005) In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro 19:975–983
Carlson C, Hussain SM, Schrand AM, Brandich-Stolle LK, Hess KL, Jones RL, Schlager JJ (2008) Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. J Phys Chem 112:13608–13619
Vinardell MP (2005) In vitro cytotoxicity of nanoparticles in mammalian germ-line stem cell. Toxicol Sci 88:285–286
Hsin Y, Chen C, Huang S, Shih T, Lai P, Chueh PJ (2008) The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett 179:130–139
Rogers EJ, Hsief SF, Organti N, Schmidt D, Bello D (2008) A high throughput in vitro analytical approach to screen for oxidative stress potential exerted by nanomaterials using a biologically relevant matrix: human blood serum. Toxicol In Vitro 22:1639–1647
Arora S, Jain J, Rajwade J, Paknikar K (2008) Interactions of silver nanoparticles with primary mouse fibroblast cells. Toxicol Appl Pharmacol 236(3):310–318
Arora S, Jain J, Rajwade J, Paknikar K (2009) Cellular responses induced by silver nanoparticles: in vitro studies. Toxicol Lett 179(2):93–100
Ahamed M, Karns M, Goodson M, Rowe J, Hussain SM, Schlager JJ, Hong Y (2008) DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. Toxicol Appl Pharm 233:404–410
Ahamed M, Posgai R, Gorey TJ, Nielsen M, Hussain SM, Rowe JJ (2010) Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster. Toxicol Appl Pharmacol Toxicol 242(3):263–269
Kim S, Choi EJ, Choi J, Chung K, Park K, Yi J (2009) Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. Toxicol In Vitro 23:1076–1084
Zanette C, Pelin M, Crosera M, Adami G, Bovenzi M, Larese FF, Florio C (2011) Silver nanoparticles exert a long-lasting antiproliferative effect on human keratinocyte HaCaT cell line. Toxicol In Vitro 25(5):1053–1060
Singh N, Manshian B, Jenkins GJ, Griffiths SM, Williams PM, Maffeis TG, Wright CJ, Doak SH (2009) NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials 30(23–24):3891–3914
Nel A, Xia T, Madler L, Li N (2006) Toxic potential of materials at the nano level. Science 311:622–627
Gutteridge JMC, Quinlan GJ (1983) Malondialdehyde formation from lipid peroxides in thiobarbituric acid test. The role of lipid radicals, iron salts and metal chelator. J Appl Biochem 5:293–299
Halliwell B (1984) Oxygen radicals: a common sense look at their nature and medical importance. Med Biol 62:71–77
Murray RK, Granner DK, Mayes PA, Rodwell VW (1988) Harper’s Biochemistry, 21st edn. Prentice Hall, Englewood Cliffs, pp 138–139
De Zwart LL, Meerman JH, Commandeur JN, Vermeulen NP.(Jan; 1999) Biomarkers of free radical damage applications in experimental animals and in humans. Free Radic Biol Med. 26(1–2):202–226. Review
Loeb WF, Quimby FW (eds) (1999) The clinical chemistry of laboratory animals. Taylor & Francis, Philadelphia
Zimmerman HJ, Seeff LB. Enzymes in hepatic disease (1970) In: Goodly EL (ed), Diagnostic enzymology, Philadelphia: Lea Febiger, pp. 1–38
Van der Zande M, Vandebriel RJ, Van Doren E, Kramer E, Herrera Rivera Z, Serrano-Rojero CS, Gremmer ER, Mast J, Peters RJ, Hollman PC, Hendriksen PJ, Marvin HJ, Peijnenburg AA, Bouwmeester H (2012) Distribution, elimination, and toxicity of silver nanoparticles and silver ions in rats after 28-day oral exposure. ACS Nano 6(8):7427–7442
Park EJ, Bae E, Yi J, Kim Y, Choi K, Lee SH, Yoon J, Lee BC, Park K (2010) Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nanoparticles. Environ Toxicol Pharmacol 30(2):162–168
Giles AR (1987) Guidelines for the use of animals in biomedical research. Thromb Haemost 58(4):1078–1084
Lawler JM, Song W, Demaree SR (2003) Hindlimb unloading increases oxidative stress and disrupt antioxidant capacity in skeletal muscle. Free Radical Biol Med 35:9–16
Reitman Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28(1):56–63
Kay HD (1930) Plasma phosphatase. I method of determination. Some properties of enzyme. J Biol Chem 89:235
Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191
Anreddy RN, Yellu NR, Devarakonda KR (2013) Oxidative biomarkers to assess the nanoparticle-induced oxidative stress. Methods Mol Biol 1028:205–219
Wu Y, Zhou Q (2013) Silver nanoparticles cause oxidative damage and histological changes in medaka (Oryzias latipes) after 14 days of exposure. Environ Toxicol Chem 32(1):165–173
Piao MJ, Kang KA, Lee IK, Kim HS, Kim S, Choi J, Hyun JW (2011) Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of mitochondria-involved apoptosis. Toxicol Lett 201:92–100
Xia T, Kovochich M, Brant J, Hotze M, Sempf J, Oberley T, Sioutas C, Yeh JI, Wiesner MR, Nei AE (2006) Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano Lett 6:1794–1807
Colvin VI (2003) The potential environmental impact of engineered nanomaterials. Nat Biotechnol 21:1166–1170
Johnston HJ, Hutchison G, Christensen FM, Peters S, Hankin S, Stone V (2010) 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. Crit Rev Toxicol 40:328–346
Roberts RA, Ganey PE, Ju C, Kamendulis LM, Rusyn I, Klaunig JE (2007) Role of kupffer cell in mediating hepatic toxicity and carcinogenesis. Toxicol Sci 96(1):2–15
Pratsinis A, Hervells P, Leroux JC, Pratsinis SE, Sotiriou GA (2013) Toxicity of silver nanoparticles in macrophages. Small 9(15):2576–2584
Hadrup N, Lam HR (2014) Oral toxicity of silver ions, silver nanoparticles and colloidal silver: a review. Regulat Toxicol Pharmacol 68:1–7
Nowack B, Krug HF, Height M (2011) 120 years of nanosilver history: implications for policy makers. Environ Sci Technol 45:1177–1183
Acknowledgments
This research was supported in part by grants from the U.S. DOD through the Engineer, Research and Development Center #W912HZ-10-2-0045 (CMCM) and in part by the NIH-Center for Environmental Health (Grant No. 2G12MD007581-16) at Jackson State University.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Patlolla, A.K., Hackett, D. & Tchounwou, P.B. Silver nanoparticle-induced oxidative stress-dependent toxicity in Sprague-Dawley rats. Mol Cell Biochem 399, 257–268 (2015). https://doi.org/10.1007/s11010-014-2252-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-014-2252-7