Israa F Mosa, Mokhtar Youssef, Thanaa Shalaby, Osama F Mosa


Silver nanoparticles (AgNPs) are being used extensively for biomedical purposes regarding to their broad antimicrobial activity, however their toxicity has been addressed in only few studies. In the present study, we aimed to prepare and characterize AgNPs, investigate their adverse effect on liver and kidney functions, and also elucidate the hepato-nephro protective ability of tannic acid in male rats. The obtained results showed that AgNPs caused oxidative stress throughout the induction of thiobarbituric acid-reactive substances (TBARS) and the reduction of the activities of antioxidant enzymes (GST, SOD, CAT, GPx) and the levels of glutathione. Hepatic markers enzymes (AST, ALT, ALP, ACP, LDH and GGT), total bilirubin, urea, creatinine and lipid profile were increased, while hematological parameters were decreased. Histopathological investigations indicated marked degeneration of hepatocytes, endothelial cells of renal which with its role has confirmed the hepatotoxicity and nephrotoxicity induced by AgNPs. The presence of tannic acid along with AgNPs showed obvious improvements in the injured liver and kidney tissues. The protective effect of tannic acid against the toxicity of AgNPs might be due to its antioxidant properties and scavenging abilities against active free radicals.


Silver nanoparticles, Tannic acid, nanotoxicology, Hepatotoxicity, renal damage, Reactive oxygen species, DNA oxidation, oxidative stress, histopathological architecture

Full Text:



Wu J, Zheng Y, Song W, Luan J, Wen X, Wu Z, et al. In situ synthesis of silver-nanoparticles/bacterial cellulose composites for slow-released antimicrobial wound dressing. Carbohydrate Polymers. 2014; 102: 762-71.

Galdiero S, Falanga A, Vitiello M, Cantisani M, Marra V, Galdiero M. Silver nanoparticles as potential antiviral agents. Molecules. 2011; 16(10): 8894-918.

Monteiro DR, Silva S, Negri M, Gorup LF, de Camargo ER, Oliveira R, et al. Antifungal activity of silver nanoparticles in combination with nystatin and chlorhexidine digluconate against Candida albicans and Candida glabrata biofilms. Mycoses. 2013; 56(6): 672-80.

Mijnendonckx K, Leys N, Mahillon J, Silver S, Van Houdt R. Antimicrobial silver: uses, toxicity and potential for resistance. Biometals. 2013; 26(4): 609-21.

Chen X, Schluesener HJ.Nanosilver: a nanoproduct in medical application. Toxicol Lett. 2008; 176(1): 1–12.

Wei L, Lu J, Xu H, Patel A, Chen ZS, Chen G. Silver nanoparticles: synthesis, properties, and therapeutic applications. Drug Discovery Today. 2015; 20(5): 595-601.

Benn T, Cavanagh B, Hristovski K, Posner JD, Westerhoff P. The release of nanosilver from consumer products used in the home. Journal of Environmental Quality. 2010; 39(6): 1875-82.

Massarsky A, Trudeau VL, Moon TW. Predicting the environmental impact of nanosilver. Environ Toxicol Pharmacol. 2014; 38(3): 861-73.

Ebabe Elle R, Gaillet S, Vidé J, Romain C, Lauret C, Rugani N, et al. Dietary exposure to silver nanoparticles in Sprague–Dawley rats: Effects on oxidative stress and inflammation. Food Chem Toxicol. 2013; 60: 297-301.

Schins RPF, Knaapen AM. Genotoxicity of poorly soluble particles. Inhalation Toxicology. 2007; 19(suppl 1): 189-98.

Hadrup N, Lam HR. Oral toxicity of silver ions, silver nanoparticles and colloidal silver- a review. Regul Toxicol Pharmacol. 2014; 68(1): 1-7.

McShan D, Ray PC, Yu H. Molecular toxicity mechanism of nanosilver. J Food Drug Anal. 2014; 22(1): 116–27.

Reidy B, Haase A, Luch A, Dawson KA, Lynch I. Mechanisms of silver nanoparticle release, transformation and toxicity: a critical review of current knowledge and recommendations for future studies and applications. Materials. 2013; 6(6): 2295-350.

Di Meo S, Reed TT, Venditti P, Victor MV. Harmful and Beneficial Role of ROS. Oxid Med Cell Longev. 2016;2016.

Nićiforović N, Mihailović V, Mašković P, Solujić S, Stojković A, Muratspahić DP. Antioxidant activity of selected plant species; potential new sources of natural antioxidants. Food Chem Toxicol. 2010; 48(11): 3125-30.

Crozier A, Jaganath IB, Clifford MN. Dietary phenolics: Chemistry, bioavailability and effects on health. Nat Prod Rep. 2009; 26(8): 1001-43.

Wang YH, Wan ZL, Yang XQ, Wang JM, Guo J, Lin Y. Colloidal complexation of zein hydrolysate with tannic acid: Constructing peptides-based nanoemulsions for alga oil delivery. Food Hydrocolloids. 2016; 54(part A): 40-8.

Sahiner N, Sagbas S, Aktas N, Silan C. Inherently antioxidant and antimicrobial tannic acid release from poly (tannic acid) nanoparticles with controllable degradability. Colloid Surf B: Biointerfaces. 2016; 142: 334-43.

Tikoo K, Sane MS, Gupta C. Tannic acid ameliorates doxorubicin-induced cardiotoxicity and potentiates its anti-cancer activity: potential role of tannins in cancer chemotherapy. Toxicol Appl Pharmacol. 2011; 251(3): 191-200.

Halkes CJM, Van Dijk H, De Jaegere PT, Plokker HWM, van Der Helm Y, Erkelens DW, et al. Postprandial increase of complement component 3 in normolipidemic patients with coronary artery disease: effects of expanded-dose simvastatin. Arterioscler Thromb Vasc Biol. 2001; 21(9), 1526-30.

Xiao H, Liu B, Mo H, Liang G. Comparative evaluation of tannic acid inhibiting α-glucosidase and trypsin. Food Res Int. 2015; 76(3): 605-10.

Fang N, Lee H, Sun C, Zhang X. Sub–diffraction-limited optical imaging with a silver superlens. Science. 2005; 308(5721): 534-7.

Sharma HS, Ali SF, Hussain SM, Schlager JJ, Sharma A. Influence of engineered nanoparticles from metals on the blood-brain barrier permeability, cerebral blood flow, brain edema and neurotoxicity. An experimental study in the rat and mice using biochemical and morphological approaches. J Nanosci Nanotechnol. 2009; 9(8): 5055-72.

Ahmad ST, Sultana S. Tannic acid mitigates cisplatin-induced nephrotoxicity in mice. Hum Exp Toxicol. 2012; 31(2): 145-56.

Tappel AL, Zalkin H. Inhibition of lipid peroxidation in mitochondria by vitamin E. Archives of Biochemistry and Biophysics. 1959; 80(2): 333-6.

Mishra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. JBC. 1972; 247: 3170-5.

Chiu DTY, Stults FH, Tappel AL. Purification and properties of rat lung soluble glutathione peroxidase. Biochim Biophys Acta. 1976; 445(3): 558-66.

Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. JBC. 1974; 249: 7130-9.

Luck H. Catalase. In: Bergmayer, M. V. (Ed.), Method of Enzymatic Analysis. Verlag Chemic. Academic Press, New. 1974; 885.

Jollow DJ, Michell JR, Zampaglionic N, Gillete JR. Bromoibenzene-induced Liver necrosis: Protective role of glutathione and evidence for 3,4-Bromobenzene oxide as hepatotoxic metabolite. Pharmacology. 1974; 11: 151-69.

Drury RA, Wallington EA, Carleton S. Histological Techniques, fifth ed., Oxford University Press, London, New York, Toronto. 1980; 241-2.

SAS, Statistical Analysis System. SAS Procedure Guide. Release 6.03 Edition. SAS Institute Inc., Cary, Nc, U.S.A. 1998.

Duncan DB. Multiple range and multiple F tests. Biometrics. 1955; 11(1): 1-42.

Garcia T, Lafuente D, Blanco J, Sanchez DJ, Sirvent JJ, Domingo JL et al. Oral subchronic exposure to silver nanoparticles in rats. Food Chem Toxicol. 2016; 92: 177-87.

Kovvuru P, Mancilla PE, Shirode AB, Murray TM, Begley TJ, Reliene R. Oral ingestion of silver nanoparticles induces genomic instability and DNA damage in multiple tissues. Nanotoxicology. 2015; 9(2): 162-71.

Sarhan OMM, Hussein RM. Effects of intraperitoneally injected silvernanoparticles on histological structures and blood parameters in the albino rat. Int J Nanomedicine. 2014; 9: 1505-17.

Burrell RE. A scientific perspective on the use of topical silver preparations. Ostomy Wound Manage. 2003; 49: 19-24.

Toh HS, Batchelor-Mcauley C, Tschulik K, Compton RG. Chemical interactions between silver nanoparticles and thiols: a comparison of mercaptohexanol against cysteine. Science China Chemistry. 2014;57(9): 1199-210.

Nemenqani D, El-Gharib O, Ahmed AM, Baiuomy AR. The protective effects of antioxidant (vitamin C) against hepatic oxidative damage induced by zinc oxide nanoparticals. IRJABS. 2015; 9(4): 502-9.

Wang J, Asbach C, Fissan H, Hülser T, Kuhlbusch TA, Thompson D, et al. How can nanobiotechnology oversight advance science and industry: examples from environmental, health, and safety studies of nanoparticles (nano-EHS). J Nanopart Res. 2011; 13(4): 1373-87.

He W, Zhou YT, Wamer WG, Boudreau MD, Yin JJ. Mechanisms of the pH dependent generation of hydroxyl radicals and oxygen induced by Ag nanoparticles. Biomaterials. 2012; 33(30): 7547-55.

Yang EJ, Kim S, Kim JS, Choi IH. Inflammasome formation and IL-1β release by human blood monocytes in response to silver nanoparticles. Biomaterials. 2012; 33(28): 6858-67.

Rahman F, Chowdhury S, Rahman MM, Ahmed D, Hossain A. Antimicrobial resistance pattern of gram-negative bacteria causing urinary tract infection. Stamford journal of pharmaceutical sciences. 2009; 2(1): 44-50.

Loeschner K, Hadrup N, Qvortrup K, Larsen A, Gao X, Vogel U, et al. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate. Particle Fibre Toxicology. 2011; 8(1): 18.

Casas-Grajales S, Muriel P. Antioxidants in liver health. World J Gastrointest Pharmacol Ther. 2015; 6(3): 59-72.

Skalska J, Dabrowska-Bouta B, Struzynska L. Oxidative stress in rat brain but not in liver following oral administration of a low dose of nanoparticulate silver. Food Chem Toxicol. 2016; 97: 307-15.

Yang ST, Wang X, Jia G, Gu Y, Wang T, Nie H, et al. Long-term accumulation and low toxicity of single-walled carbon nanotubes in intravenously exposed mice. Toxicol Lett. 2008; 181(3): 182-9.

Kim S, Choi JE, Choi J, Chung KH, Park K, Yi J, et al. Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. Toxicology in vitro. 2009; 23(6): 1076-84.

Recknagel RO, Glende Jr EA, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther. 1989; 43(1): 139-54.

Adeyemi OS, Whiteley CG. Interaction of nanoparticles with arginine kinase from Trypanosoma brucei: kinetic and mechanistic evaluation. International journal of biological macromolecules. 2013; 62: 450-6.

Guyton AC, Hall JE. Dominant role of the kidney in long-term regulation of arterial pressure and in hypertension: the integrated system for pressure control. Guyton & Hall: Textbook of Medical Physiology. 2000; 10: 195-209.

Venkatesan N, Punithavathi D, Arumugam V. Curcumin prevents adriamycin nephrotoxicity in rats. Br J Pharmacol. 2000; 129(2): 231–4.

Braydich-Stolle L, Hussain S, Schlager JJ, Hofmann MC. In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci. 2005; 88(2): 412-9.

Albendea CD, Gómez-Trullén EM, Fuentes-Broto L, Miana-Mena FJ, Millán-Plano S, Reyes-Gonzales MC, et al. Melatonin reduces lipid and protein oxidative damage in synaptosomes due to aluminium. J Trace Elem Med Bio. 2007; 21(4): 261-8.

Ene-ojo AS, Chinedu EA, Yakasai FM. Toxic effects of sub-chronic administration of chloroform extract of Artemisia maciverae Linn on the kidney of Swiss albino rats. Int J Biochem Res Rev. 2013;3(2):119-28.

Sarkar D, Latif SA, Aich J, Uddin MM. Studies on serum Creatinine and Creatinine clearance in hypertensive patients. JBSP. 2006; 1: 19-26.

Adeyemi OS, Sulaiman FA. Biochemical and morphological changes in Trypanosoma brucei brucei-infected rats treated with homidium chloride and diminazene aceturate. Journal of basic and clinical physiology and pharmacology. 2012; 23(4): 179-83.

Adeyemi OS, Akanji MA. Psidium guajava leaf extract. Effects on rat serum homeostasis and tissue morphology. Comparative Clinical Pathology. 2010; 21(4): 401-7.

Naghsh N, Mashayekh AM, Khodadadi S. Effects of silver nanoparticle on lactate dehydrogenase activity and histological changes of heart tissue in male wistar rats. Journal of Fasa University of Medical Sciences. 2013; 2(4): 303-7.

Lovrić J, Bazzi HS, Cuie Y, Fortin GR, Winnik FM, Maysinger D. Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots. J Mol Med. 2005; 83(5): 377-85.

Sharma V, Shukla RK, Saxena N, Parmar D, Das M, Dhawan A. DNA damaging potential of zinc oxide nanoparticles in human epidermal cells. Toxicol Lett. 2009; 185(3): 211-8.

Arora S, Jain J, Rajwade JM, Paknikar KM. Cellular responses induced by silver nanoparticles: in vitro studies. Toxicol Lett. 2008; 179(2): 93-100.

Tiwari R, Singh RD, Khan H, Gangopadhyay S, Mittal S, Singh V, et al. Oral subchronic exposure to silver nanoparticles causes renal damage through apoptotic impairment and necrotic cell death. Nanotoxicology. 2017; 11(5): 671-86.

Meng J, Ji Y, Liu J, Cheng X, Guo H, Zhang W, et al. Using gold nanorods core/silver shell nanostructures as model material to probe biodistribution and toxic effects of silver nanoparticles in mice. Nanotoxicology. 2014; 8(6): 686-96.

Guo H, Zhang J, Boudreau M, Meng J, Yin JJ, Liu J, et al. Intravenous administration of silver nanoparticles causes organ toxicity through intracellular ROS-related loss of interendothelial junction. Particle Fibre Toxicology. 2016; 13(1): 21.

Vivarelli M, Massella L, Ruggiero B, Emma F. Minimal Change Disease. Clin J Am Soc Nephrol. 2016; 27: 1811-22.

Kroemer G, El-Deiry WS, Golstein P, Peter ME, Vaux D, Vandenabeele P, et al. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death Differ. 2005; 12(suppl 2): 1463-7.

Li L, Wu H, Peijnenburg WJ, Van Gestel CA. Both released silver ions and particulate Ag contribute to the toxicity of AgNPs to earthworm Eisenia fetida. Nanotoxicology. 2015; 9(6): 792-801.

Uchiumi F, Sato T, Tanuma SI. Identification and characterization of a tannic acid-responsive negative regulatory element in the mouse mammary tumor virus promoter. J Biol Chem. 1998; 273(20): 12499-508.

Andrade RG, Dalvi LT, Silva JMC, Lopes GK, Alonso A, Hermes-Lima M. The antioxidant effect of tannic acid on the in vitro copper-mediated formation of free radicals. Arch Biochem Biophys. 2005; 437(1): 1-9.



  • There are currently no refbacks.

Copyright (c) 2019 Israa F Mosa

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.