Histopathological effects of nanosilver (Ag-NPs) in liver after dermal exposure during wound healing


1 Biology Department, Faculty of Sciences, University of Shahrekord, Shahrekord, Iran

2 Genetics Department, Faculty of Sciences, University of Shahrekord, Shahrekord, Iran

3 Department of Anatomical and Histological Science of Basic Sciences, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran



With the advent of nanotechnology, significant progress has been made in the area of nanoscale materials such as nanosilver (Ag-Nps). These nanoparticles have a wide range of applications and been used for antimicrobial purposes for more than a century. However, little
attention has been paid to the toxicity of nanosilver wound dressing. This study was designed to investigate the possible histopathological toxicity of Ag-NPs in liver of mice during wound healing.
Materials and Methods:
A group of 50 female BALB/c mice of about 8 weeks were randomly divided into two groups: Ag-NPs and control groups (n=25). After creating similar wound on the backs of all animals, the wound bed was treated in Ag-NPs group, with a volume of 50 microliters of the nanosilver solution (10ppm) ,and in control group, with the same amount of distilled water. The experiment lasted for 14 days. Histopathaological samplings of liver were conducted on days 2, 7 and 14 of the experiment.
Histopathological studies demonstrated time-dependent changes in mice liver treated with Ag-NPs compared to control group. Some changes include dilation in central venous, hyperemia, cell swelling, increase of Kupffer and inflammatory cells.
This study suggests that use of nanosilver for wound healing may cause a mild toxicity, as indicated by time-dependent toxic responses in liver tissue. However, this issue will have to be considered more extensively in further studies


1. Ruvollo-Filho AC, Camargo ERd, Barbosa DB. The growing importance of materials that prevent microbial adhesion: antimicrobial effect of medical devices containing silver. Int J Antimicrob Ag. 2009; 34(2): 103-110.

2. Choi O, Clevenger TE, Deng B, Surampalli RY, Ross Jr L, Hu Z. Role of sulfide and ligand strength in controlling nanosilver toxicity. Water Res. 2009; 43(7): 1879-1886.

3. Benn T, Cavanagh B, Hristovski K, Posner JD, Westerhoff P. The release of nanosilver from consumer products used in the home. J Environ Qual. 2010; 39(6): 1875-1882.

4. Theivasanthi T, Alagar M. Anti-bacterial Studies of Silver Nanoparticles. arXiv preprint arXiv:11010348. 2011.

5. Linkov I, Satterstrom FK, Corey LM. Nanotoxicology and nanomedicine: making hard decisions. Nanomedicine: Nanotechnol Biol Med. 2008; 4(2): 167-171.

6. Seaton A, Donaldson K. Nanoscience, nanotoxicology, and the need to think small. Lancet. 2005; 365(9463): 923-924.

7. Rastogi ID. Nanotechnology: safety paradigms. J Toxi-col Environ Health. 2012; 4(1): 1-12.

8. Kim YS, Song MY, Park JD, Song KS, Ryu HR, Chung YH, et al. Subchronic oral toxicity of silver nanoparticles. Part Fibre toxicol. 2010; 7(1): 20.

9. Lara HH, Garza-Treviٌo EN, Ixtepan-Turrent L, Singh DK. Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds. J Nanobiotechnology. 2011; 9(1): 30.

10. Pronk M, Wijnhoven SW, Bleeker E, Heugens EH, Peijnenburg WJ, Luttik R, et al. Nanomaterials under REACH. Nanosilver as a case study. RIVM rapport 601780003. 2009. Available from URL: http://www.rivm.nl/bibliotheek/rapporten/601780003.pdf.

11. Knetsch ML, Koole LH. New strategies in the development of antimicrobial coatings: the example of increasing usage of silver and silver nanoparticles. Polymers. 2011; 3(1): 340-366.

12. Tang J, Xi T. Status of biological evaluation on silver nanoparticles. Sheng wu yi xue gong cheng xue za zhi. 2008; 25(4): 958-961.

13. Hussain S, Hess K, Gearhart J, Geiss K, Schlager J. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol in Vitro. 2005; 19(7): 975-984.

14. Kim S, Choi JE, Choi J, Chung K-H, Park K, Yi J, et al. Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. Toxicol in vitro. 2009; 23(6): 1076-1084.

15. Miura N, Shinohara Y. Cytotoxic effect and apoptosis induction by silver nanoparticles in HeLa cells. Biochem Biophys Res Commun. 2009; 390(3): 733-737.

16. Song X-l, Li B, Xu K, Liu J, Ju W, Wang J, et al. Cytotoxicity of water-soluble mPEG-SH-coated silver nanoparticles in HL-7702 cells. Cell Biol Toxicol. 2012; 28(4): 225-237.

17. Kvitek L, Vanickova M, Panacek A, Soukupova J, Dittrich M, Valentova E, et al. Initial study on the toxicity of silver nanoparticles (NPs) against Paramecium caudatum. J Phys Chem C. 2009; 113(11): 4296-4300.

18. Takenaka S, Karg E, Roth C, Schulz H, Ziesenis A, Heinzmann U, et al. Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect. 2001; 109(Suppl 4): 547–551.

19. Lee Y, Kim P, Yoon J, Lee B, Choi K, Kil K-H, et al. Serum kinetics, distribution and excretion of silver in rabbits following 28 days after a single intravenous injection of silver nanoparticles. Nanotoxicology. 2013; 7(6): 1120-1130.

20. Arora S, Jain J, Rajwade J, Paknikar K. Interactions of silver nanoparticles with primary mouse fibroblasts and liver cells. Toxicol Appl Pharmacol. 2009; 236(3): 310-318.

21. Bidgoli SA, Mahdavi M, Rezayat SM, Korani M, Amani A, Ziarati P. Toxicity Assessment of Nanosilver Wound Dressing in Wistar Rat. Acta Med Iran. 2013; 51(4): 203-208.

22. Loghman A, Sohrabi H, Djeddi A, Mortazavi P. Histopathologic and apoptotic effect of nanosilver in liver of broiler chickens. Afr J Biotechnol. 2012; 11(22): 6207-6211.

23. Koohi Mk, Hejazy M, Asadi F, Asadian P. Assessment of dermal exposure and histopathologic changes of different sized nano-silver in healthy adult rabbits. J Phys: Conf Ser. 2011; 304 012028. Available from URL: doi:10.1088/1742-6596/304/1/012028.

24. Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, et al. Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats. Inhal Toxicol. 2008; 20(6): 575-583.

25. Sardari RRR, Zarchi SR, Talebi A, Nasri S, Imani S, Khoradmehr A, et al. Toxicological effects of silver nanoparticles in rats. Afr J Microbiol Res. 2012; 6(27): 5587-5593.

26. Yousef J, Hendi H, Hakami FS, Awad MA, Alem AF, Hendi AA, et al. Toxicity of Silver Nanoparticles after Injected Intraperitoneally in Rats. J Am Sci. 2012; 8(3): 589-593.

27. Sadauskas E, Wallin H, Stoltenberg M, Vogel U, Doering P, Larsen A, et al. Kupffer cells are central in the removal of nanoparticles from the organism. Part Fibre Toxicol. 2007; 4(10): 1-7.

28. Korani M, Rezayat S, Gilani K, Bidgoli SA, Adeli S. Acute and subchronic dermal toxicity of nanosilver in guinea pig. Int J Nanomedicine. 2011; 6(1): 855–862.

29. Xia T, Kovochich M, Brant J, Hotze M, Sempf J, Oberley T, et al. Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. Nano letters. 2006; 6(8): 1794-1807.