Skip to main content
SpringerLink
Log in

Health risk assessments of lithium titanate nanoparticles in rat liver cell model for its safe applications in nanopharmacology and nanomedicine

  • Original Research
  • Published:
Cytotechnology Aims and scope Submit manuscript

Abstract

Due to their high chemical stability, lithium titanate (Li2TiO3) nanoparticles (LTT NPs) now are projected to be transferred into different nanotechnology areas like nano pharmacology and nano medicine. With the increased applications of LTT NPs for numerous purposes, the concerns about their potential human toxicity effects and their environmental impact are also increased. However, toxicity data for LTT NPs related to human health are very limited. Therefore we aimed to investigate toxicity potentials of various concentrations (0–1,000 ppm) of LTT NPs (<100 nm) in cultured primary rat hepatocytes. Cell viability was detected by [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT) assay and lactate dehydrogenase (LDH) release, while total antioxidant capacity (TAC) and total oxidative stress (TOS) levels were determined to evaluate the oxidative injury. DNA damage was analyzed by scoring liver micronuclei rates and by determining 8-oxo-2-deoxyguanosine (8-OH-dG) levels. The results of MTT and LDH assays showed that higher concentrations of dispersed LTT NPs (500 and 1,000 ppm) decreased cell viability. Also, LTT NPs increased TOS (300, 500 and 1,000 ppm) levels and decreased TAC (300, 500 and 1,000 ppm) levels in cultured hepatocytes. The results of genotoxicity tests revealed that LTT NPs did not cause significant increases of micronucleated hepatocytes and 8-OH-dG as compared to control culture. In conclusion, the obtained results showed for the first time that LTT NPs had dose dependent effects on oxidative damage and cytotoxicity but not genotoxicity in cultured primary rat hepatocytes for the first time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Albrecht C, Scherbart AM, van Berlo D, Braunbarth CM, Schins RPF, Scheel J (2009) Evaluation of cytotoxic effects and oxidative stress with hydroxyapatite dispersions of different physicochemical properties in rat NR8383 cells and primary macrophages. Toxicol In Vitro 23:520–530

    Article  CAS  Google Scholar 

  • Alom-Ruiz SP, Anilkumar N, Shah AM (2008) Reactive oxygen species and endothelial activation. Antioxid Redox Signal 10:1089–1100

    Article  CAS  Google Scholar 

  • Anreddy RN, Yellu NR, Devarakonda KR (2013) Oxidative biomarkers to assess the nanoparticle-induced oxidative stress. Methods Mol Biol 1028:205–219

    Article  Google Scholar 

  • Bhattacharya K, Davoren M, Boertz J, Schins RP, Hoffmann E, Dopp E (2009) Titanium dioxide nanoparticles induce oxidative stress and DNA-adduct formation but not DNA-breakage in human lung cells. Part Fibre Toxicol 6:17

    Article  Google Scholar 

  • Cai XJ, Xu YY (2011) Nanomaterials in controlled drug release. Cytotechnol 63:319–323

    Article  CAS  Google Scholar 

  • Ciofani G, Danti S, D’Alessandro D, Moscato S, Petrini M, Menciassi A (2010) Barium titanate nanoparticles: highly cytocompatible dispersions in glycol-chitosan and doxorubicin complexes for cancer therapy. Nanoscale Res Lett 5:1093–1101

    Article  CAS  Google Scholar 

  • Davis RR, Hobbs DT, Kahshaba R, Sehkar P, Seta FN, Messer RL, Lewis JB, Wataha JC (2010) Titanate particles as agents to deliver gold compounds to fibroblasts and monocytes. J Biomed Mater Res A 93:864–869

    Google Scholar 

  • ECETOC (2005) Workshop on Testing Strategies to Establish the Safety of Nanomaterials. November 2005, Barcelona, Workshop Report No: 7

  • Farrukh MA, Tan P, Adnan R (2012) Influence of reaction parameters on the synthesis of surfactant-assisted tin oxide nanoparticles. Turk J Chem 36:303–314

    CAS  Google Scholar 

  • Fehr T, Schmidbauer E (2007) Electrical conductivity of Li2TiO3 ceramics. Solid State Ion 178:35–41

    Article  CAS  Google Scholar 

  • Geyikoglu F, Turkez H (2005) Protective effect of sodium selenite on genotoxicity to human whole blood cultures induced by aflatoxin B-1. Brazil Arch Biol Technol 48:905–910

    Article  CAS  Google Scholar 

  • Ghodsi FE, Absalan H (2010) Comparative study of ZNO thin films prepared by different sol–gel route. Acta Phys Pol, A 118:659–664

    CAS  Google Scholar 

  • Grandjean-Laquerriere A, Laquerriere P, Guenounou M, Laurent-Maquin D, Phillips TM (2005) Importance of the surface area ratio on cytokines production by human monocytes in vitro induced by various hydroxyapatite particles. Biomater 26:2361–2369

    Article  CAS  Google Scholar 

  • Han SD, Campet G, Huang SY, Shasrty MCR, Portier J, Lassegues JC, Dweik HS (1995) A new method for the preparation of fine-grained SnO2 and WO3 powders: influence of the crystallite size on the electrochemical insertion of Li + in SnO2 and WO3 electrodes. Active Passive Electron Component 18:39–51

    Article  Google Scholar 

  • Hoshino T, Tanaka K, Makita J, Hashimoto T (2007) Investigation of phase transition in Li2TiO3 by high temperature X-ray diffraction. J Nuclear Mat 367:1052–1056

    Article  Google Scholar 

  • Hsin YH, Chen CF, Huang S, Shih TS, Lai PS, 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

    Article  CAS  Google Scholar 

  • Ilıcan S, Caglar Y, Caglar M (2008) Preparation and characterization of ZnO thin films deposited by sol–gel spin coating method. J Optoelectron Adv Mater 10:2578–2583

    Google Scholar 

  • Jian-wen Y, Hui Z, Haryun Z, Yarryang D, Jian L, Xuan Z (2004) Synthesis and electrochemical properties of nanocrystalline Li[Li1/3Ti3/5O4] by complex sol–gel method. Trans Nonferrous Met Soc China 14:1012–1016

    Google Scholar 

  • Kang SJ, Kim BM, Lee YJ, Chung HW (2008) Titanium dioxide nanoparticles trigger p53-mediated damage response in peripheral blood lymphocytes. Environ Mol Mutagen 49:399–405

    Article  CAS  Google Scholar 

  • Kataoka K, Yasuhiko T, Norihito K, Hideaki N, Junji A, Yasushi I, Ken-ichi O (2009) Crystal growth and structure refinement of monoclinic Li2TiO3. Mater Res Bull 44:168–172

    Article  CAS  Google Scholar 

  • Kim S, Choi JE, Choi J, Chung KH, Park K, Yi J (2009) Oxidative stress-dependent toxicity of silver nanoparticles in human hepatoma cells. Toxicol In Vitro 23:1076–1084

    Article  CAS  Google Scholar 

  • Klien K, Godniccvar J (2012) Genotoxicity of metal nanoparticles: focus on in vivo studies. Arh Hig Rada Toksikol 63:133–145

    Article  CAS  Google Scholar 

  • Knaapen AM, Borm PJ, Albrecht C, Schins RP (2004) Inhaled particles and lung cancer. Part A: Mechanisms. Int J Cancer 109:799–809

    CAS  Google Scholar 

  • Lanone S, Rogerieux F, Geys J, Dupont A, Maillot-Marechal E, Boczkowski J (2009) Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines. Part Fibre Toxicol 6:14–19

    Article  Google Scholar 

  • Lewinski N, Colvin V, Drezek R (2008) Cytotoxicity of nanoparticles. Small 4:26–49

    Article  CAS  Google Scholar 

  • Li SQ, Zhu RR, Zhu H, Xue M, Sun XY, Yao SD, Wang SL (2008) Nanotoxicity of TiO2 nanoparticles to erythrocyte in vitro. Food Chem Toxicol 46:3626–3631

    Article  CAS  Google Scholar 

  • Lin LN, Liu Q, Song L, Liu FF, Sha JX (2010) Recent advances in nanotechnology based drug delivery to the brain. Cytotechnol 62:377–380

    Article  CAS  Google Scholar 

  • Liu X, Sun J (2010) Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kB pathways. Biomater 31:8198–8209

    Article  CAS  Google Scholar 

  • Lu PJ, Ho IC, Lee TC (1998) Induction of sister chromatid exchanges and micronuclei by titanium dioxide in Chinese hamster ovary-K1cells. Mutat Res 414:15–20

    Article  CAS  Google Scholar 

  • Lu J, Caiyun N, Qing P, Yadong L (2012) Single crystalline lithium titanate nanostructure with enhanced rate performance for lithium ion battery. J Power Sources 202:246–252

    Article  CAS  Google Scholar 

  • Magrez A, Horváth L, Smajda R, Salicio V, Pasquier N, Forró L, Schwaller B (2009) Cellular toxicity of TiO2-based nanofilaments. ACS Nano 3:2274–2280

    Article  CAS  Google Scholar 

  • Manke A, Wang L, Rojanasakul Y (2013) Mechanisms of nanoparticle-induced oxidative stress and toxicity. BioMed Res Int 2013:942916, doi: 10.1155/2013/942916

  • Nakagawa Y, Wakuri S, Sakamoto K, Tanaka N (1997) The photo genotoxicity of titanium dioxide particles. Mutat Res 394:125–132

    Article  CAS  Google Scholar 

  • Oesterling E, Chopra N, Gavalas V, Arzuaga X, Lim EJ, Sultana R (2008) Alumina nanoparticles induce expression of endothelial cell adhesion molecules. Toxicol Lett 178:160–166

    Article  CAS  Google Scholar 

  • Pan Y, Leifert A, Ruau D, Neuss S, Bornemann J, Schmid G (2009) Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. Small 5:2067–2076

    Article  CAS  Google Scholar 

  • Poulter KF, Pryde JA (1968) Chemisorption of hydrogen on rhenium. Brit J Appl Phys Ser 1:169

    Google Scholar 

  • Ramesh M, Turner LF, Yadav R, Rajan TV, Vella AT, Kuhn LT (2007) Effects of the physico-chemical nature of two biomimetic crystals on the innate immune response. Int Immunopharmacol 7:1617–1629

    Article  CAS  Google Scholar 

  • Riehemann K, Schneider SW, Luger TA, Godin B, Ferrari M, Fuchs H (2009) Nanomedicine-challenge and perspectives. Angew Chem Int Ed Engl 48:872–897

    Article  CAS  Google Scholar 

  • Rothen-Rutishauser B, Mühlfeld C, Blank F, Musso C, Gehr P (2007) Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model. Part Fibre Toxicol 4:9

    Article  Google Scholar 

  • Schanen BC, Karakoti AS, Seal S, Drake DR, Warren WL, Self WT (2009) Exposure to titanium dioxide nanomaterials provokes inflammation of an in vitro human immune construct. ACS Nano 3:2523–2532

    Article  CAS  Google Scholar 

  • Schins RP, Lightbody JH, Borm PJ, Shi T, Donaldson K, Stone V (2004) Inflammatory effects of coarse and fine particulate matter in relation to chemical and biological constituents. Toxicol Appl Pharmacol 195:1–11

    Article  CAS  Google Scholar 

  • Schmid O, Moller W, Semmler-Behnke M, Ferron GA, Karg E, Lipka J, Schulz H, Kreyling WG, Stoeger T (2009) Dosimetry and toxicology of inhaled ultrafine particles. Biomarkers 14:67–73

    Article  CAS  Google Scholar 

  • Simbula G, Columbano A, Ledda-Columbano GM, Sanna L, Deidda M, Diana A (2007) Increased ROS generation and p53 activation in alpha-lipoic acidinduced apoptosis of hepatoma cells. Apoptosis 12:113–123

    Article  CAS  Google Scholar 

  • Sioutas C, Delfino RJ, Singh M (2005) Exposure assessment for atmospheric Ultrafine Particles (UFPs) and implications in epidemiologic research. Environ Health Perspect 113:947–955

    Article  Google Scholar 

  • Sisman T, Turkez H (2010) Toxicologic evaluation of imazalil with particular reference to genotoxic and teratogenic potentials. Toxicol Ind Health 26:641–648

    Article  CAS  Google Scholar 

  • Song Y, Li X, Du X (2009) Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma. Eur Respir J 34:559–567

    Article  CAS  Google Scholar 

  • Suzuki H, Takasawa H, Kobayashi K, Terashima Y, Shimada Y, Ogawa I, Tanaka J, Imamura T, Miyazaki A, Hayashi M (2009) Evaluation of a liver micronucleus assay with 12 chemicals using young rats (II): a study by the Collaborative Study Group for the Micronucleus Test/Japanese Environmental Mutagen Society-Mammalian Mutagenicity Study Group. Mutagen 24:9–16

  • Tsuchiya K, Nakamichi M, Nagao Y, Enoeda M, Osaki T, Tanaka S, Kawamura H (2001) In-situ tritium recovery experiments of blanket in-pile mockup with Li2TiO3 pebble bed in Japan. J Nuclear Sci Technol 38:996–999

    Article  CAS  Google Scholar 

  • Turkez H (2008) Effects of boric acid and borax on titanium dioxide genotoxicity. J Appl Toxicol 28:658–664

    Article  CAS  Google Scholar 

  • Turkez H (2011) The role of ascorbic acid on titanium dioxide-induced genetic damage assessed by the comet assay and cytogenetic tests. Exp Toxicol Pathol 63:453–457

    Article  CAS  Google Scholar 

  • Turkez H, Geyikoglu F (2007) An in vitro blood culture for evaluating the genotoxicity of titanium dioxide: the responses of antioxidant enzymes. Toxicol Ind Health 23:19–23

    Article  CAS  Google Scholar 

  • Turkez H, Geyikoglu F (2010) Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood. Cytotechnol 62:157–165

    Article  CAS  Google Scholar 

  • Turkez H, Sisman T (2007) Anti-genotoxic effect of hydrated sodium calcium aluminosilicate on genotoxicity to human lymphocytes induced by aflatoxin B1. Toxicol Ind Health 23:83–89

    Article  CAS  Google Scholar 

  • Turkez H, Togar B (2010) The genotoxic and oxidative damage potential of olanzapine in vitro. Toxicol Ind Health 26:583–588

    Article  CAS  Google Scholar 

  • Turkez H, Geyikoglu F, Keles MS (2005) Biochemical response to colloidal bismuth subcitrate: dose-time effect. Biol Trace Elem Res 105:151–158

    Article  Google Scholar 

  • Turkez H, Geyikoglu F, Tatar A, Keleş S, Ozkan A (2007) Effects of some boron compounds on peripheral human blood. Z Naturforsch C 62:889–896

    Article  CAS  Google Scholar 

  • Turkez H, Geyikoglu F, Tatar A, Keles MS, Kaplan I (2012) The effects of some boron compounds against heavy metal toxicity in human blood. Exp Toxicol Pathol 64:93–101

    Article  CAS  Google Scholar 

  • Turkez H, Cakmak B, Celik K (2013a) Evaluation of the potential in vivo genotoxicity of Tungsten (VI) oxide nanopowder for human health. Key Engineering Mater 543:89–92

    Article  Google Scholar 

  • Turkez H, Celik K, Cakmak B (2013b) Biosafety evaluation of nanoparticles in view of genotoxicity and carcinogenicity studies: a systematic review. Key Eng Mater 543:200–203

    Article  Google Scholar 

  • Unfried K, Albrecht C, Klotz LO, von Mikecz A, Grether-Beck S, Schins RPF (2007) Cellular responses to nanoparticles: target structures and mechanisms. Nanotoxicol 1:52–71

    Article  CAS  Google Scholar 

  • Wang Y, Aker WG, Hwang HM, Yedjou CG, Yu H, Tchounwou PB (2011) A study of the mechanism of in vitro cytotoxicity of metal oxide nanoparticles using catfish primary hepatocytes and human HepG2 cells. Sci Total Environ 409:4753–4762

    Article  CAS  Google Scholar 

  • Wataha JC, Hobbs DT, Wong JJ, Dogan S, Zhang H, Chung KH, Elvington MC (2010) Titanates deliver metal ions to human monocytes. J Mater Sci Mater Med 21:1289–1295

    Article  CAS  Google Scholar 

  • Xia T, Kovochich M, Brant J (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

    Article  CAS  Google Scholar 

  • Xiangwei W, Zhaoyin W, Bin L, Xiaogang X (2008) Sol–gel synthesis and sintering of nano-size Li2TiO3 powder. Material Lett 62:837–839

    Article  Google Scholar 

  • Xu A, Chai Y, Hei TK (2009) Genotoxic responses to titanium dioxide nanoparticles and fullerene in gptdelta transgenic MEF cells. Part Fibre Toxicol 6:3

    Article  Google Scholar 

  • Xu Z, Zhang YL, Song C, Wu LL, Gao HW (2012) Interactions of hydroxyapatite with proteins and its toxicological effect to zebrafish embryos development. PLoS ONE 7:e32818

    Article  CAS  Google Scholar 

  • Zhang ZG, Li ZH, Mao XZ, Wang WC (2011) Advances in bone repair with nanobiomaterials: mini-review. Cytotechnol 63:437–443

    Article  CAS  Google Scholar 

  • Zhang J, Song W, Guo J, Zhang J, Sun Z, Li L, Ding F, Gao M (2013) Cytotoxicity of different sized TiO2 nanoparticles in mouse macrophages. Toxicol Ind Health 29:523–533

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum, Turkey

    Hasan Turkez

  2. Department of Physics, K. K. Education Faculty, Atatürk University, 25240, Erzurum, Turkey

    Erdal Sönmez

  3. Dipartimento di Farmacia, Università “G. D’Annunzio”, Via dei Vestini 31, 66100, Chieti, Italy

    Antonio Di Stefano

  4. Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, 21526, Egypt

    Yousef I. Mokhtar

Authors
  1. Hasan Turkez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erdal Sönmez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonio Di Stefano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yousef I. Mokhtar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hasan Turkez.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Turkez, H., Sönmez, E., Di Stefano, A. et al. Health risk assessments of lithium titanate nanoparticles in rat liver cell model for its safe applications in nanopharmacology and nanomedicine. Cytotechnology 68, 291–302 (2016). https://doi.org/10.1007/s10616-014-9780-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-014-9780-6

Keywords

Search

Navigation