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Modulation of liver and kidney toxicity by herb Withania somnifera for silver nanoparticles: a novel approach for harmonizing between safety and use of nanoparticles

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Abstract

In the present study, toxicity of nanoparticles is evaluated for assessing their effect on liver and kidney. We have synthesized highly mono-disperse spherical and rod-shaped silver nanoparticles using reverse microemulsion and aqueous phase methods. These were characterized by UV–vis spectrophotometer, dynamic light scattering, and transmission electron microscope confirming the formation of different sizes of spherical-shaped and rod-shaped silver nanoparticles (Ag NPs). Acute toxicity of different shapes and sizes of Ag NPs and their modulations by using Withania somnifera were evaluated through biochemical and histopathological changes in liver and kidney tissues of Wistar rats. We also evaluated cytotoxicity in specific murin macrophages through confocal microscopy. Cytotoxicity analysis indicates that median lethal dose (LD50) for 20, 50, and 100-nm size spherical and 100-nm rod-shaped Ag NPs was 0.25, 0.35, 0.35, and 0.35 mg/ml, respectively. We also calculated clinically important protein concentration to illustrate the efficacy of Ag nanomaterials. These studies indicated that 20, 50, and 100-nm spherical Ag NPs (35 mg/kg, 23 days) increased the biochemically important enzymes and substrate levels glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), creatinine, and urea concentration in serum, showing liver and kidney tissue damage. After 23 days of treatment of Ag NPs (20, 50, and 100 nm spherical), along with W. somnifera, toxicity of Ag NPs significantly decreased and marginalized. However, no significant changes were observed for 100-nm rod-shaped Ag NPs on normal liver and kidney architecture. Given their low toxic effects and high uptake efficiency, these have a promising potential as to lower the toxicity of Ag NPs.

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Abbreviations

SGOT:

Serum glutamic oxaloacetic transaminase

SGPT:

Serum glutamic pyruvic transaminase

ALP:

Alkaline phosphatase

BUN:

Blood urea nitrogen

TEM:

Transmission electron microscopy

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

Ag NPs:

Silver nanoparticles

LD50 :

Median lethal dose

DLS:

Dynamic light scattering

AOT:

Sodium bis(2-ethylhexyl) sulfosuccinate

EDTA:

Ethylenediaminetetracetic acid

References

  • Abou-Douh AM (2002) New withanolides and other constituents from the fruit of Withania somnifera. Arch Pharm 335:267–276

    Article  CAS  Google Scholar 

  • Ahamed M, Alsalhi MS, Siddiqui MKJ (2010) Silver nanoparticle applications and human health. Clin Chim Acta 411:1841

    Article  CAS  PubMed  Google Scholar 

  • Alarco EI, Udekwu K, Skog M et al (2012) The biocompatibility and antibacterial properties of collagen-stabilized photochemically prepared silver nanoparticles. Biomaterials 33:4947

    Article  Google Scholar 

  • Allain CC, Poon LS, Chan CSG et al (1978) Enzymatic determination of total serum urea. Clin Chem 20:470–475

    Google Scholar 

  • Anwar MF, Yadav D, Kapoor S et al (2013) Comparison of antibacterial activity of Ag nanoparticles synthesized from leaf extract of Parthenium hystrophorus L in aqueous media and gentamicin sulphate: in-vitro. Drug Dev Ind Pharm. doi:10.3109/03639045.2013.845840

    Google Scholar 

  • Bhattacharya A, Ghosal S, Bhattacharya SK (2001) Anti-oxidant effect of Withania somnifera glycol withanolides in chronic foot shock stress-induced perturbations of oxidative free radical scavenging enzymes and lipid peroxidation in rat frontal cortex and striatum. J Ethno Pharmacol 74:1–6

    Article  CAS  Google Scholar 

  • Budhiraja RD, Sudhir S, Garg KN et al (1987) BC: review of biological activity of withanolides. J Sci Ind Res 46:488–491

    CAS  Google Scholar 

  • Carlson C, Hussain SM, Schrand AM et al (2008) Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. The J Physic Chem B 112:13608–13619

    Article  CAS  Google Scholar 

  • Chaudhary G, Sharma U, Jagannathan NR et al (2003) Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats. Clin Exp Pharmacol Physiol 30:399–404

    Article  CAS  PubMed  Google Scholar 

  • Cheng D, Yang J, Zhao Y (2004) Antibacterial materials of silver nanoparticles application in medical appliances and appliances for daily use. Chin Med Equip J 4:26–32

    Google Scholar 

  • Choi O, Clevenger TE, Deng B et al (2009) Role of sulfide and ligand strength in controlling nanosilver toxicity. Water Res 43:1879–1886

    Article  CAS  PubMed  Google Scholar 

  • Cohen MS, Stern JM, Vanni AJ et al (2007) In vitro analysis of a nanocrystalline silver-coated surgical mesh. Surg Infect 8:397–403

    Article  Google Scholar 

  • Dhalla NS, Sastry NS, Malhotra CL (1961) Chemical studies of the Withania somnifera. J Pharm Sci 50:876–877

    Article  CAS  PubMed  Google Scholar 

  • Edwards-Jones V (2009) The benefits of silver in hygiene, personal care and health care. Lett Appl Microbiol 49:147–152

    Article  CAS  PubMed  Google Scholar 

  • Fabian H, Martin JD, Rothen-Rutishauser CB et al (2013) Exposure of silver-nanoparticles and silver-ions to lung cells in vitro at the air-liquid interface. Part Fibre Toxicol 10:11

    Article  Google Scholar 

  • He BL, Tanm JJ, Kong YL et al (2004) Synthesis of size controlled Ag nanoparticles. J Mol Catal A: Chem 221:121–126

    Article  CAS  Google Scholar 

  • Huiliang C, Xuanyong L, Fanhao M et al (2011) Biological actions of silver nanoparticles embedded in titanium controlled by micro-galvanic effects. Biomaterials 32:693–705

    Article  Google Scholar 

  • Husdan H, Rapoport A (1968) Estimation of creatinine by the Jaffe reaction: a comparison of three methods. Clin Chem 14:222–238

    CAS  PubMed  Google Scholar 

  • Kandil FE, Elsayeh NH, Abou-Douh AM et al (1994) Flavonol glycosides and phenolics from Withania somnifera. Phytochemistry 37:1215–1216

    Article  CAS  Google Scholar 

  • Kim WY, Kim J, Park JD et al (2009) Histological study of gender differences in accumulation of silver nanoparticles in kidneys of Fischer 344 rats. J Toxicol Environ Health A 72:1279–84

    Article  CAS  PubMed  Google Scholar 

  • King PRM, King EJ (1954) Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrene. J Clin Path 7:322–326

    Article  PubMed Central  PubMed  Google Scholar 

  • Kulkarni RR, Patki PS, Jog VP et al (1991) Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 33:91–95

    Article  CAS  PubMed  Google Scholar 

  • Kumar OA, Jyothirmayee G, Tata SS (2011) In vitro plant regeneration from leaf explants of Withania somnifera (L) Dunal (Ashwaganda)—an important medicinal plant. Res Biotech 2:34–3

    Google Scholar 

  • Lam PK, Chan ES, Ho WS et al (2004) In vitro cytotoxicity testing of a nanocrystalline silver dressing (Acticoat) on cultured keratinocytes. Br J Biomed Sci 61:125–127

    CAS  PubMed  Google Scholar 

  • Lankveld DP, Oomen AG, Krystek P et al (2010) The kinetics of the tissue distribution of silver nanoparticles of different sizes. Biomaterials 31:8350–8361

    Article  CAS  PubMed  Google Scholar 

  • Lansdown A (2006) Silver in health care: antimicrobial effects and safety in use. Curr Probl Dermatol 33:17–34

    Article  CAS  PubMed  Google Scholar 

  • Larissa VS, Andrea AD, Jong SK et al (2011) Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model. Part Fibre Toxicol 8:5

    Article  Google Scholar 

  • Linda CS, Edgar G, Andreas S et al (2011) Shape matters: effects of silver nanospheres and wires on human alveolar epithelial cells. Part Fibre Toxicol 8:36

    Article  Google Scholar 

  • Liu L, Yang J, Xie J et al (2013) The potent antimicrobial properties of cell penetrating peptide-conjugated silver nanoparticles with excellent selectivity for gram-positive bacteria over erythrocytes. Nanoscale 5:3834–40

    Article  CAS  PubMed  Google Scholar 

  • Lu W, Senapati D, Wang S et al (2010) Effect of surface coating on the toxicity of silver nanomaterials on human skin keratinocytes. Chem Phys Lett 487:92

    Article  CAS  Google Scholar 

  • Muangman P, Chuntrasakul C, Silthram S et al (2006) Comparison of efficacy of 1% silver sulfadiazine and Acticoat for treatment of partial-thickness burn wounds. J Med Assoc Thai 89:953–958

    PubMed  Google Scholar 

  • Nel A, Xia T, Madler L et al (2006) Toxic potential of materials at the nanolevel. Science 311:622–627

    Article  CAS  PubMed  Google Scholar 

  • Nel A, Xia T, Meng H et al (2012) Nanomaterial toxicity testing in the 21st century: use of a predictive toxicological approach and high throughput screening. Acc Chemi Res. doi:10.1021/ar300022h

    Google Scholar 

  • Nittala SS, Lavie S (1988) Chemistry and genetics of withanolides in Withania somnifera hybrids. Phytochemistry 20:2741–2748

    Article  Google Scholar 

  • Niyaz A, Siddiqui EN (2014) Seed germination of Withania somnifera (L.) Dunal. Eur J Med Plants 4:920–926

    Article  CAS  Google Scholar 

  • Oberdorster G, Maynard A, Donaldson K et al (2005) Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2:8

    Article  PubMed Central  PubMed  Google Scholar 

  • Oberpichler H, Sauer D, Rossberg C et al (1990) PAF antagonist ginkgolide B reduces postischemic neuronal damage in rat brain hippocampus. J Cereb Blood Flow Metab 10:133

    Article  CAS  PubMed  Google Scholar 

  • Panda S, Kar A (1997) Evidence for free radical scavenging activity of Ashwagandha root powder in mice. Ind J Physio Pharmaco 41:424–426

    CAS  Google Scholar 

  • Park E, Bae E (2010) Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nanoparticles. Environ Toxicol Pharm 30:162–168

    Article  CAS  Google Scholar 

  • Park J, Lim DH, Lim HJ et al (2011) Size dependent macrophage responses and toxicological effects of Ag nanoparticles. Chem Commun 47:4382

    Article  CAS  Google Scholar 

  • Reitman S, Frankel S (1957) Glutamic—pyruvate transaminase assay by colorimetric method. Am J Clin Path 28:56

    CAS  PubMed  Google Scholar 

  • Sharma M (2010) Understanding the mechanism of toxicity of carbon nanoparticles in humans in the new millennium: a systemic review. Indian J Occup Environ Med 14:3–5

    Article  PubMed Central  PubMed  Google Scholar 

  • Sharma V, Sharma S, Pracheta et al (2011) Withania somniforma: a rejuvinating Ayurvedic medicinal herb for the treatment of various human ailments. Intl J Pharm Tech Res 3:187–192

    Google Scholar 

  • Shayestech TH, Khajavi F, Ghasemi H et al (2014) Effects of silver nanoparticle (Ag NP) on oxidative stress, liver function in rat: hepatotoxic or hepatoprotective? Issues Biol Sci Pharma Res 2:40–44

    Google Scholar 

  • Singh B, Saxena AK, Chandan BK et al (2001) Hepatoprotective activity of indigtone—a bioactive fraction from Indigo feratinctoria Linn. Phytother Res 15:294–7

    Article  CAS  PubMed  Google Scholar 

  • Singh B, Chandan BK, Gupta DK (2003) Adaptogenic activity of a novel withanolide-free aqueous fraction from the roots of Withania somnifera Dun. (Part II). Phytother Res 17:531–6

    Article  CAS  PubMed  Google Scholar 

  • Wagner H, Norr H, Winterhoff H (1994) Plantadaptogens. Phytomedicine 1:63–76

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Qiao X, Chen J, Ding S (2005) Preparation of silver nanoparticles by chemical reduction method. Coll Surf A Physico Chem Eng Asp 256:111–115

    Article  CAS  Google Scholar 

  • Wilhelm M, Zhao CL, Wang Y et al (1991) Poly(styrene-ethylene oxide) block copolymer micelle formation in water: a fluorescence probe study. Macromolecules 24:1033–1040

    Article  CAS  Google Scholar 

  • Yadav D, Chaudhary AA, Garg V et al (2013) In vitro toxicity and antidiabetic activity of a newly developed polyherbal formulation (MAC-ST/001) in streptozotocin-induced diabetic Wistar rats. Protoplasma 250:741–749

    Article  CAS  PubMed  Google Scholar 

  • Yong SK, Moon YS, Jung DP et al (2010) Subchronic oral toxicity of silver nanoparticles. Part Fibre Toxicol 7:20

    Article  Google Scholar 

  • Zhang Y, Sun J (2007) A study on the bio-safety for nano-silver as anti-bacterial materials. Chin J Med Instrum 31:35–38

    CAS  Google Scholar 

Download references

Acknowledgments

Authors are thankful to Dr. G. N. Qazi, Vice Chancellor, Jamia Hamdard, New Delhi, for providing working facilities. Authors are also grateful to the Department of Science and Technology (DST), Government of India, for financial support.

Conflict of interests

The author(s) declare that they have no competing interests.

Authors’ contributions

Ag NPs were synthesized, characterized, and studied in vivo by MFA and DY. Statistical analyses were done by MFA, DY, RKK, JC, SR, IA, and MS that were involved in the inception and planning of the project and in the preparation of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Mohd Samim.

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Handling Editor: Reimer Stick

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Anwar, M.F., Yadav, D., Rastogi, S. et al. Modulation of liver and kidney toxicity by herb Withania somnifera for silver nanoparticles: a novel approach for harmonizing between safety and use of nanoparticles. Protoplasma 252, 547–558 (2015). https://doi.org/10.1007/s00709-014-0701-5

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