Skip to main content

Advertisement

SpringerLink
Log in

Effects of Titanium Dioxide Nanoparticles Isolated from Confectionery Products on the Metabolic Stress Pathway in Human Lung Fibroblast Cells

  • Published:
Archives of Environmental Contamination and Toxicology Aims and scope Submit manuscript

Abstract

Titanium dioxide (TiO2) is a common additive in many foods, pigments, personal care products, and other consumer products used in daily life. Despite the widespread use of nanoscale TiO2 and composites of nanoscale TiO2 in the food industry, there is a serious lack of awareness of the toxicity of TiO2 nanoparticles (NPs) among consumers and manufacturers. There is an urgent need for toxicological studies of TiO2 NPs. TiO2 food additives separated from marketed foods were characterized by transmission electron microscopy. In addition, the effects of TiO2 NPs on metabolic stress in WI-38 cells were analyzed. Cell viability, total ROS, mitochondrial transmembrane potential (ΔψM), cell cycle, and metabolism-related gene expression were analyzed. The results indicate that TiO2 NPs have a significant concentration-dependent toxic effect in lung cells. The ΔψM, the intracellular ROS level, and the stages of the WI-38 cell cycle were altered by increasing TiO2 concentrations after exposure for 24 and 48 h relative to the control. Cytochrome P450 1A, GSTM3, and glutathione S-transferase A4 upregulation in response to the TiO2 NPs was observed. These findings suggest that the toxicity of TiO2 from confectionery products in WI-38 cells may be mediated through an increase in oxidative stress. The results of this study clearly demonstrate the nanotoxicological effects of TiO2 on WI-38 cells and will be useful for nanotoxicological indexing.

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
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Allouni ZE, Hol PJ, Cauqui MA, Gjerdet NR, Cimpan MR (2012) Role of physicochemical characteristics in the uptake of TiO2 nanoparticles by fibroblasts. Toxicol In Vitro 26:469–479

    Article  CAS  Google Scholar 

  • Attik G, Brown R, Jackson P, Creutzenberg O, Aboukhamis I, Rihn BH (2008) Internalization, cytotoxicity, apoptosis, and tumor necrosis factor-alpha expression in rat alveolar macrophages exposed to various dusts occurring in the ceramics industry. Inhal Toxicol 20:1101–1112

    Article  CAS  Google Scholar 

  • Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, Cogliano V (2006) Carcinogenicity of carbon black, titanium dioxide, and talc. Lancet Oncol 7:295–296

    Article  Google Scholar 

  • Becker S, Soukup JM, Gallagher JE (2002) Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages. Toxicol In Vitro 16:209–218

    Article  CAS  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 

  • Blagosklonny MV, El-Deiry WS (1996) In vitro evaluation of a p53-expressing adenovirus as an anti-cancer drug. Int J Cancer 67:386–392

    Article  CAS  Google Scholar 

  • Cha MH, Rhim T, Kim KH, Jang AS, Paik YK, Park CS (2007) Proteomic identification of macrophage migration-inhibitory factor upon exposure to TiO2 particles. Mol Cell Proteomics 6:56–63

    Article  CAS  Google Scholar 

  • Chen J, Zhou H, Santulli AC, Wong SS (2010) Evaluating cytotoxicity and cellular uptake from the presence of variously processed TiO2 nanostructured morphologies. Chem Res Toxicol 23:871–879

    Article  CAS  Google Scholar 

  • Choksi AN, Poonawalla T, Wilkerson MG (2010) Nanoparticles: a closer look at their dermal effects. J Drugs Dermatol 9:475–481

    Google Scholar 

  • Drumm K, Buhl R, Kienast K (1999) Additional NO2 exposure induces a decrease in cytokine specific mRNA expression and cytokine release of particle and fibre exposed human alveolar macrophages. Eur J Med Res 4:59–66

    CAS  Google Scholar 

  • Epstein HA (2011) Nanotechnology in cosmetic products. Skinmed 9:109–110

    Google Scholar 

  • Ferin J, Leach LJ (1973) The effect of SO2 on lung clearance of TiO2 particles in rats. Am Ind Hyg Assoc J 34:260–263

    Article  CAS  Google Scholar 

  • Ferin J, Leach LJ (1976) The effect of amostie and chrysotile asbestos on the clearance of TiO2 particles from the lung. Environ Res 12:250–254

    Article  CAS  Google Scholar 

  • Frick R, Muller-Edenborn B, Schlicker A, Rothen-Rutishauser B, Raemy DO, Gunther D et al (2011) Comparison of manganese oxide nanoparticles and manganese sulfate with regard to oxidative stress, uptake and apoptosis in alveolar epithelial cells. Toxicol Lett 205:163–172

    Article  CAS  Google Scholar 

  • Gao Y, Gopee NV, Howard PC, Yu LR (2011) Proteomic analysis of early response lymph node proteins in mice treated with titanium dioxide nanoparticles. J Proteomics 74:2745–2759

    Article  CAS  Google Scholar 

  • Guo J, Padilla RJ, Ambrose W, De Kok IJ, Cooper LF (2007) The effect of hydrofluoric acid treatment of TiO2 grit blasted titanium implants on adherent osteoblast gene expression in vitro and in vivo. Biomaterials 28:5418–5425

    Article  CAS  Google Scholar 

  • Hackenberg S, Friehs G, Froelich K, Ginzkey C, Koehler C, Scherzed A et al (2010) Intracellular distribution, geno- and cytotoxic effects of nanosized titanium dioxide particles in the anatase crystal phase on human nasal mucosa cells. Toxicol Lett 195:9–14

    Article  CAS  Google Scholar 

  • Halamoda KB, Chapuis Bernasconi C, Guney-Ayra S, Juillerat-Jeanneret L (2012) Induction of oxidative stress, lysosome activation and autophagy by nanoparticles in human brain-derived endothelial cells. Biochem J 441:813–821

    Article  Google Scholar 

  • Hendren CO, Mesnard X, Droge J, Wiesner MR (2011) Estimating production data for five engineered nanomaterials as a basis for exposure assessment. Environ Sci Technol 45:2562–2569

    Article  CAS  Google Scholar 

  • Horie M, Nishio K, Fujita K, Kato H, Endoh S, Suzuki M et al (2010) Cellular responses by stable and uniform ultrafine titanium dioxide particles in culture-medium dispersions when secondary particle size was 100 nm or less. Toxicol In Vitro 24:1629–1638

    Article  CAS  Google Scholar 

  • Horie M, Fukui H, Endoh S, Maru J, Miyauchi A, Shichiri M et al (2012) Comparison of acute oxidative stress on rat lung induced by nano and fine-scale, soluble and insoluble metal oxide particles: NiO and TiO2. Inhal Toxicol 24:391–400

    Article  CAS  Google Scholar 

  • Hots T (2001) The effects of ozone and toxic air particles on airway function in mice. Fiziol Zh 47:63–68

    Google Scholar 

  • Huang S, Chueh PJ, Lin YW, Shih TS, Chuang SM (2009) Disturbed mitotic progression and genome segregation are involved in cell transformation mediated by nano-TiO2 long-term exposure. Toxicol Appl Pharmacol 241:182–194

    Article  CAS  Google Scholar 

  • Hussain S, Thomassen LC, Ferecatu I, Borot MC, Andreau K, Martens JA et al (2010) Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells. Part Fibre Toxicol 7:10

    Article  Google Scholar 

  • Hussain S, Vanoirbeek JA, Luyts K, De Vooght V, Verbeken E, Thomassen LC et al (2011) Lung exposure to nanoparticles modulates an asthmatic response in a mouse model. Eur Respir J 37:299–309

    Article  CAS  Google Scholar 

  • Ichiura H, Kitaoka T, Tanaka H (2003) Removal of indoor pollutants under UV irradiation by a composite TiO2-zeolite sheet prepared using a papermaking technique. Chemosphere 50:79–83

    Article  CAS  Google Scholar 

  • International Agency for Research on Cancer (2006) Titanium dioxide classified as possibly carcinogenic to humans. IARC, Lyons, France. Available at: http://www.ccohs.ca/headlines/text186.html. Accessed 21 May 2013

  • Kalfa OM, Yalcinkaya O, Turker AR (2009) Synthesis of nano B2O3/TiO2 composite material as a new solid phase extractor and its application to preconcentration and separation of cadmium. J Hazard Mater 166:455–461

    Article  CAS  Google Scholar 

  • Kim IS, Baek M, Choi SJ (2010) Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells. J Nanosci Nanotechnol 10:3453–3458

    Article  CAS  Google Scholar 

  • Kitchin KT, Prasad RY, Wallace K (2011) Oxidative stress studies of six TiO(2) and two CeO(2) nanomaterials: immuno-spin trapping results with DNA. Nanotoxicology 5:546–556

    Article  CAS  Google Scholar 

  • Kocbek P, Teskac K, Kreft ME, Kristl J (2010) Toxicological aspects of long-term treatment of keratinocytes with ZnO and TiO2 nanoparticles. Small 6:1908–1917

    Article  CAS  Google Scholar 

  • LeBlanc AJ, Moseley AM, Chen BT, Frazer D, Castranova V, Nurkiewicz TR (2010) Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism. Cardiovasc Toxicol 10:27–36

    Article  CAS  Google Scholar 

  • Lee KP, Henry NW 3rd, Trochimowicz HJ, Reinhardt CF (1986) Pulmonary response to impaired lung clearance in rats following excessive TiO2 dust deposition. Environ Res 41:144–167

    Article  CAS  Google Scholar 

  • Lee YS, Yoon S, Yoon HJ, Lee K, Yoon HK, Lee JH et al (2009) Inhibitor of differentiation 1 (Id1) expression attenuates the degree of TiO2-induced cytotoxicity in H1299 non-small cell lung cancer cells. Toxicol Lett 189:191–199

    Article  CAS  Google Scholar 

  • Li HC, Zhang YM, Sun HP (2012) Effect of diameter-controlled Ti-TiO2 nanotubes on the adhesion of osteoblast and fibroblast. Zhonghua Kou Qiang Yi Xue Za Zhi 47:122–126

    CAS  Google Scholar 

  • Lomer MC, Thompson RP, Commisso J, Keen CL, Powell JJ (2000) Determination of titanium dioxide in foods using inductively coupled plasma optical emission spectrometry. Analyst 125:2339–2343

    Article  CAS  Google Scholar 

  • Lomer MC, Harvey RS, Evans SM, Thompson RP, Powell JJ (2001) Efficacy and tolerability of a low microparticle diet in a double blind, randomized, pilot study in Crohn’s disease. Eur J Gastroenterol Hepatol 13:101–106

    Article  CAS  Google Scholar 

  • Lomer MC, Thompson RP, Powell JJ (2002) Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn’s disease. Proc Nutr Soc 61:123–130

    Article  Google Scholar 

  • Ma L, Liu J, Li N, Wang J, Duan Y, Yan J et al (2010) Oxidative stress in the brain of mice caused by translocated nanoparticulate TiO2 delivered to the abdominal cavity. Biomaterials 31:99–105

    Article  CAS  Google Scholar 

  • Maatta J, Majuri ML, Luukkonen R, Lauerma A, Husgafvel-Pursiainen K, Alenius H et al (2005) Characterization of oak and birch dust-induced expression of cytokines and chemokines in mouse macrophage RAW 264.7 cells. Toxicology 215:25–36

    Article  Google Scholar 

  • McIntyre RA (2012) Common nano-materials and their use in real world applications. Sci Prog 95:1–22

    Article  CAS  Google Scholar 

  • National Institute for Occupational Safety and Health (2011) Outlines guidance on handling titanium dioxide (TiO2). http://www.cdc.gov/niosh/NPPM/upd-04-18-11.html. Accessed 4 Feb 2013

  • Osman IF, Jacob BK, Anderson D (2011) Effect of nanoparticles on human cells from healthy individuals and patients with respiratory diseases. J Biomed Nanotechnol 7:26–27

    Article  CAS  Google Scholar 

  • Petkovic J, Zegura B, Stevanovic M, Drnovsek N, Uskokovic D, Novak S et al (2011) DNA damage and alterations in expression of DNA damage responsive genes induced by TiO2 nanoparticles in human hepatoma HepG2 cells. Nanotoxicology 5:341–353

    Article  CAS  Google Scholar 

  • Powell JJ, Harvey RS, Ashwood P, Wolstencroft R, Gershwin ME, Thompson RP (2000) Immune potentiation of ultrafine dietary particles in normal subjects and patients with inflammatory bowel disease. J Autoimmun 14:99–105

    Article  CAS  Google Scholar 

  • Pujalte I, Passagne I, Brouillaud B, Treguer M, Durand E, Ohayon-Courtes C et al (2011) Cytotoxicity and oxidative stress induced by different metallic nanoparticles on human kidney cells. Part Fibre Toxicol 8:10

    Article  CAS  Google Scholar 

  • Ramkumar KM, Manjula C, Gnanakumar G, Kanjwal MA, Sekar TV, Paulmurugan R et al (2012) Oxidative stress-mediated cytotoxicity and apoptosis induction by TiO2 nanofibers in HeLa cells. Eur J Pharm Biopharm 81:324–333

    Article  CAS  Google Scholar 

  • Rossi EM, Pylkkanen L, Koivisto AJ, Nykasenoja H, Wolff H, Savolainen K et al (2010) Inhalation exposure to nanosized and fine TiO2 particles inhibits features of allergic asthma in a murine model. Part Fibre Toxicol 7:35

    Article  CAS  Google Scholar 

  • Sayes CM, Wahi R, Kurian PA, Liu Y, West JL, Ausman KD, Warheit DB et al (2006) Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol Sci 92:174–185

    Article  CAS  Google Scholar 

  • Scarino A, Noel A, Renzi PM, Cloutier Y, Vincent R, Truchon G et al (2012) Impact of emerging pollutants on pulmonary inflammation in asthmatic rats: ethanol vapors and agglomerated TiO2 nanoparticles. Inhal Toxicol 24:528–538

    Article  CAS  Google Scholar 

  • Schilling K, Bradford B, Castelli D, Dufour E, Nash JF, Pape W et al (2010) Human safety review of “nano” titanium dioxide and zinc oxide. Photochem Photobiol Sci 9:495–509

    Article  CAS  Google Scholar 

  • Shukla RK, Kumar A, Pandey AK, Singh SS, Dhawan A (2011) Titanium dioxide nanoparticles induce oxidative stress-mediated apoptosis in human keratinocyte cells. J Biomed Nanotechnol 7:100–101

    Article  CAS  Google Scholar 

  • Singh S, Shi T, Duffin R, Albrecht C, van Berlo D, Hohr D et al (2007) Endocytosis, oxidative stress and IL-8 expression in human lung epithelial cells upon treatment with fine and ultrafine TiO2: role of the specific surface area and of surface methylation of the particles. Toxicol Appl Pharmacol 222:141–151

    Article  CAS  Google Scholar 

  • Skocaj M, Filipic M, Petkovic J, Novak S (2011) Titanium dioxide in our everyday life: is it safe? Radiol Oncol 45:227–247

    Article  CAS  Google Scholar 

  • Teow Y, Asharani PV, Hande MP, Valiyaveettil S (2011) Health impact and safety of engineered nanomaterials. Chem Commun (Camb) 47:7025–7038

    Article  CAS  Google Scholar 

  • Wamer WG, Yin JJ, Wei RR (1997) Oxidative damage to nucleic acids photosensitized by titanium dioxide. Free Radic Biol Med 23:851–858

    Article  CAS  Google Scholar 

  • Weir A, Westerhoff P, Fabricius L, Hristovski K, von Goetz N (2012) Titanium dioxide nanoparticles in food and personal care products. Environ Sci Technol 46:2242–2250

    Article  CAS  Google Scholar 

  • Wokovich A, Tyner K, Doub W, Sadrieh N, Buhse LF (2009) Particle size determination of sunscreens formulated with various forms of titanium dioxide. Drug Dev Ind Pharm 35:1180–1189

    Article  CAS  Google Scholar 

  • Yu JX, Li TH (2011) Distinct biological effects of different nanoparticles commonly used in cosmetics and medicine coatings. Cell Biosci 1:19

    Article  Google Scholar 

  • Zhang Q, Kusaka Y, Sato K, Nakakuki K, Kohyama N, Donaldson K (1998) Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals. J Toxicol Environ Health A 53:423–438

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Zhao J, Bowman L, Zhang X, Vallyathan V, Young SH, Castranova V et al (2009) Titanium dioxide (TiO2) nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid and mitochondrial pathways. J Toxicol Environ Health A 72:1141–1149

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by National Science, Technology and Innovation Plan (NSTIP) strategic technologies Program No. BIO-981-10 in the Kingdom of Saudi Arabia.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Nanobiotechnology and Molecular Biology Research Laboratory, Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, P.O. Box 2460, Riyadh, 11451, Kingdom of Saudi Arabia

    Vaiyapuri Subbarayan Periasamy, Jegan Athinarayanan, Ahmed M. Al-Hadi, Fahad Al Juhaimi & Ali A. Alshatwi

Authors
  1. Vaiyapuri Subbarayan Periasamy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jegan Athinarayanan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed M. Al-Hadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fahad Al Juhaimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ali A. Alshatwi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali A. Alshatwi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Periasamy, V.S., Athinarayanan, J., Al-Hadi, A.M. et al. Effects of Titanium Dioxide Nanoparticles Isolated from Confectionery Products on the Metabolic Stress Pathway in Human Lung Fibroblast Cells. Arch Environ Contam Toxicol 68, 521–533 (2015). https://doi.org/10.1007/s00244-014-0109-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00244-014-0109-4

Keywords

Search

Navigation