Skip to main content

Advertisement

SpringerLink
Log in

Thermal stress and TiO2 nanoparticle–induced oxidative DNA damage and apoptosis in mouse hippocampus

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Titanium dioxide (nano-TiO2) is used abundantly in various industrial products and novel medical therapies. In addition, the impact of climate change on the health and safety will undoubtedly increase in the future. However, the effects of exposure to these nanoparticles and heat stress on hippocampal DNA damage and apoptosis remain unclear. This study was conducted to evaluate the DNA damage and apoptosis in the hippocampal tissue and the physiological responses in mice induced by intraperitoneal (i.p.) administration of TiO2 nanoparticles (NPs) and heat stress for 14 consecutive days. The results showed that heat stress and TiO2-NPs were induced in the mouse hippocampus that led to hippocampal reactive oxygen species generation, oxidative damage of DNA, and apoptosis in a partly dose-dependent manner, especially at very hot temperature. High doses of nanosized TiO2 and severe heat stress significantly damaged the function of the hippocampus, as shown in the comet assay and apoptosis tests. The results of this study may provide data for appropriate measures to control and assess the risk of nano-TiO2 and thermal stress hazards to human health, especially workers. Safety guidelines and policies should be considered when handling nanomaterials in a hot environment.

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

Similar content being viewed by others

Data availability

The data that support this study are available from the corresponding author upon reasonable request.

References

  • Adusumilli NC, Mordorski B, Nosanchuk J, Friedman JM, Friedman AJ (2021) Curcumin nanoparticles as a photoprotective adjuvant. Exp Dermatol 30(5):705–709

    Article  CAS  Google Scholar 

  • Aghmasheh S, Ostad SN, Abedi A (2020) Pharmacological properties of pt (ii) and pt (iv) complexes with 2, 2′-dipyridylamine; the comparative in vitro thereof. Cell Biochem Biophys 78(4):521–529

    Article  CAS  Google Scholar 

  • Aliebrahimi S, Kouhsari SM, Arab SS, Shadboorestan A, Ostad SN (2018) Phytochemicals, withaferin a and carnosol, overcome pancreatic cancer stem cells as c-met inhibitors. Biomed Pharmacother 106:1527–1536

    Article  CAS  Google Scholar 

  • Attia H, Nounou H, Shalaby M (2018) Zinc oxide nanoparticles induced oxidative DNA damage, inflammation and apoptosis in rat’s brain after oral exposure. Toxics 6(2):29

    Article  Google Scholar 

  • Council NR (2011) Guide for the care and use of laboratory animals: Eighth edition. Washington, DC: The National Academies Press

  • Cui Y, Gong X, Duan Y, Li N, Hu R, Liu H, Hong M, Zhou M, Wang L, Wang H (2010) Hepatocyte apoptosis and its molecular mechanisms in mice caused by titanium dioxide nanoparticles. J Hazard Mater 183(1-3):874–880

    Article  CAS  Google Scholar 

  • Dawood M, Koshio S, Zaineldin A, Van Doan H, Ahmed H, Elsabagh M, Abdel-Daim M (2019) An evaluation of dietary selenium nanoparticles for red sea bream (Pagrus major) aquaculture: growth, tissue bioaccumulation, and antioxidative responses. Environ Sci Pollut Res Int 26(30):30876–30884

    Article  CAS  Google Scholar 

  • Das S, Das J, Samadder A, Boujedaini N, Khuda-Bukhsh AR (2012) Apigenin-induced apoptosis in a375 and a549 cells through selective action and dysfunction of mitochondria. Exp Biol Med 237(12):1433–1448

    Article  CAS  Google Scholar 

  • DeBow S, Colbourne F (2003) Brain temperature measurement and regulation in awake and freely moving rodents. Methods 30(2):167–171

    Article  CAS  Google Scholar 

  • Dehghan H, Habibi E, Habibi P, Maracy MR (2013) Validation of a questionnaire for heat strain evaluation in women workers. Int J Prev Med 4(6):631

    Google Scholar 

  • El-Said KS, Ali EM, Kanehira K, Taniguchi A (2014) Molecular mechanism of DNA damage induced by titanium dioxide nanoparticles in toll-like receptor 3 or 4 expressing human hepatocarcinoma cell lines. J Nanobiotechnology 12:48

    Article  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicologic pathology 35(4):495–516

    Article  CAS  Google Scholar 

  • Gao G, Ze Y, Li B, Zhao X, Zhang T, Sheng L, Hu R, Gui S, Sang X, Sun Q (2012) Ovarian dysfunction and gene-expressed characteristics of female mice caused by long-term exposure to titanium dioxide nanoparticles. J Hazard Mater 243:19–27

    Article  CAS  Google Scholar 

  • Ghanbarian M, Nicknam MH, Mesdaghinia A, Yunesian M, Hassanvand MS, Soleimanifar N, Rezaei S, Atafar Z, Ghanbarian M, Faraji M (2019) Investigation and comparison of in vitro genotoxic potency of pm 10 collected in rural and urban sites at tehran in different metrological conditions and different seasons. Biol Trace Elem Res 189(1):301–310

    Article  CAS  Google Scholar 

  • Glei M, Schneider T, Schlörmann W (2016) Comet assay: an essential tool in toxicological research. Arch Toxicol 90(10):2315–2336

    Article  CAS  Google Scholar 

  • Golbabaei F, Heydari A, Moradi G, Dehghan H, Moradi A, Habibi P (2020) The effect of cooling vests on physiological and perceptual responses: a systematic review. Int J Occup Saf Ergon, 1-33

  • Grande F, Tucci P (2016) Titanium dioxide nanoparticles: a risk for human health? Mini Rev Med Chem 16(9):762–769

    Article  CAS  Google Scholar 

  • Gui S, Zhang Z, Zheng L, Cui Y, Liu X, Li N, Sang X, Sun Q, Gao G, Cheng Z (2011) Molecular mechanism of kidney injury of mice caused by exposure to titanium dioxide nanoparticles. J Hazard Mater 195:365–370

    Article  CAS  Google Scholar 

  • Habibi P, Momeni R, Dehghan H (2015) Relationship of environmental, physiological, and perceptual heat stress indices in iranian men. Int J Prev Med 6

  • Habibi P, Moradi G, Moradi A, Golbabaei F (2021a) A review on advanced functional photonic fabric for enhanced thermoregulating performance. Environ Nanotechnol Monit Manag, 100504

  • Habibi P, Moradi G, Moradi A, Heydari A (2021b) The impacts of climate change on occupational heat strain in outdoor workers: a systematic review. Urban Clim 36:100770

    Article  Google Scholar 

  • Harikai N, Tomogane K, Miyamoto M, Shimada K, Onodera S, Tashiro S-i (2003) Dynamic responses to acute heat stress between 34 c and 38.5 c, and characteristics of heat stress response in mice. Biol Pharm Bull 26(5):701–708

    Article  CAS  Google Scholar 

  • Hu R, Gong X, Duan Y, Li N, Che Y, Cui Y, Zhou M, Liu C, Wang H, Hong F (2010) Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to tio2 nanoparticles. Biomaterials 31(31):8043–8050

    Article  CAS  Google Scholar 

  • Hu R, Zheng L, Zhang T, Gao G, Cui Y, Cheng Z, Cheng J, Hong M, Tang M, Hong F (2011) Molecular mechanism of hippocampal apoptosis of mice following exposure to titanium dioxide nanoparticles. J Hazard Mater 191(1-3):32–40

    Article  CAS  Google Scholar 

  • Jia X, Wang S, Zhou L, Sun L (2017) The potential liver, brain, and embryo toxicity of titanium dioxide nanoparticles on mice. Nanoscale Res Lett 12(1):1–14

    Article  Google Scholar 

  • Kantidze O, Velichko A, Luzhin A, Razin S (2016) Heat stress-induced DNA damage. Acta Naturae 8(2 (29))

  • Kjellstrom T, Lemke B, Venugopal V. (2013). Occupational health and safety impacts of climate conditions Climate vulnerability: understanding and addressing threats to essential resources (Vol. 1, pp. 145-156): Elsevier Inc.

  • Li N, Duan Y, Hong M, Zheng L, Fei M, Zhao X, Wang J, Cui Y, Liu H, Cai J (2010) Spleen injury and apoptotic pathway in mice caused by titanium dioxide nanoparticules. Toxicol Lett 195(2-3):161–168

    Article  CAS  Google Scholar 

  • Liu S, Xu L, Zhang T, Ren G, Yang Z (2010) Oxidative stress and apoptosis induced by nanosized titanium dioxide in pc12 cells. Toxicology 267(1-3):172–177

    Article  CAS  Google Scholar 

  • Ma L, Liu J, Li N, Wang J, Duan Y, Yan J, Liu H, Wang H, Hong F (2010) Oxidative stress in the brain of mice caused by translocated nanoparticulate tio2 delivered to the abdominal cavity. Biomaterials 31(1):99–105

    Article  CAS  Google Scholar 

  • Maroni P, Bendinelli P, Tiberio L, Rovetta F, Piccoletti R, Schiaffonati L (2003) In vivo heat-shock response in the brain: signalling pathway and transcription factor activation. Mol Brain Res 119(1):90–99

    Article  CAS  Google Scholar 

  • Meena R, Rani M, Pal R, Rajamani P (2012) Nano-tio2-induced apoptosis by oxidative stress-mediated DNA damage and activation of p53 in human embryonic kidney cells. Appl Biochem Biotechnol 167(4):791–808

    Article  CAS  Google Scholar 

  • Mohammed E, Safwat G (2013) Assessment of the ameliorative role of selenium nanoparticles on the oxidative stress of acetaminophen in some tissues of male albino rats. Beni-Seuf Univ J Appl 2(2):80–85

    Google Scholar 

  • Mohammed E, Safwat G (2020) Grape seed proanthocyanidin extract mitigates titanium dioxide nanoparticle (TiO2-NPs)–induced hepatotoxicity through TLR-4/NF-κB signaling pathway. Biol Trace Elem Res 196(2):579–589

    Article  CAS  Google Scholar 

  • Mohammed E, Hashem K, Abdelazem A, Foda F (2020) Prospective protective effect of ellagic acid as a SIRT1 activator in iron oxide nanoparticle-induced renal damage in rats. Biol Trace Elem Res 198(1):177–188

    Article  CAS  Google Scholar 

  • Norton A, Leaman J (2004) The day after tomorrow: public opinion on climate change. MORI Social Research Institute, London

    Google Scholar 

  • Osano E, Kishi J, Takahashi Y (2003) Phagocytosis of titanium particles and necrosis in tnf-α-resistant mouse sarcoma l929 cells. Toxicol In Vitro 17(1):41–47

    Article  CAS  Google Scholar 

  • Osman IF, Najafzadeh M, Sharma V, Shukla RK, Jacob BK, Dhawan A, Anderson D (2018) Tio2 nps induce DNA damage in lymphocytes from healthy individuals and patients with respiratory diseases-an ex vivo/in vitro study. J Nanosci Nanotechnol 18(1):544–555

    Article  CAS  Google Scholar 

  • Petković J, Zegura B, Stevanović M, Drnovšek N, Uskoković D, Novak S, Filipič M (2011) DNA damage and alterations in expression of DNA damage responsive genes induced by tio2 nanoparticles in human hepatoma hepg2 cells. Nanotoxicology 5(3):341–353

    Article  Google Scholar 

  • Qian C, Wang J-Q, Song C-L, Wang L-L, Ji L-N, Chao H (2013) The induction of mitochondria-mediated apoptosis in cancer cells by ruthenium (ii) asymmetric complexes. Metallomics 5(7):844–854

    Article  CAS  Google Scholar 

  • Ryu AR, Bang IC, Lee SA, Lee MY (2016) The protective role of phytochemicals on tio2 nanoparticles-induced DNA damage in lymphocytes. J Environ Biol 37(5):913–917

    CAS  Google Scholar 

  • Shakeel M, Jabeen F, Shabbir S, Asghar MS, Khan MS, Chaudhry AS (2016) Toxicity of nano-titanium dioxide (tio 2-np) through various routes of exposure: a review. Biol Trace Elem Res 172(1):1–36

    Article  CAS  Google Scholar 

  • Sharma HS, Sharma A (2007) Nanoparticles aggravate heat stress induced cognitive deficits, blood–brain barrier disruption, edema formation and brain pathology. Prog Brain Res 162:245–273

    Article  CAS  Google Scholar 

  • Shin J, Lee E, Seo S, Kim H, Kang J, Park E (2010) Nanosized titanium dioxide enhanced inflammatory responses in the septic brain of mouse. Neuroscience 165(2):445–454

    Article  CAS  Google Scholar 

  • Shrivastava R, Raza S, Yadav A, Kushwaha P, Flora SJ (2014) Effects of sub-acute exposure to tio2, zno and al2o3 nanoparticles on oxidative stress and histological changes in mouse liver and brain. Drug Chem Toxicol 37(3):336–347

    Article  CAS  Google Scholar 

  • Varlamova E, Turovsky E, Blinova E (2021) Therapeutic potential and main methods of obtaining selenium nanoparticles. Int J Mol Sci 22(19):10808

    Article  CAS  Google Scholar 

  • Wang JJ, Sanderson BJ, Wang H (2007) Cyto-and genotoxicity of ultrafine tio2 particles in cultured human lymphoblastoid cells. Mutat Res Genet Toxicol Environ Mutagen 628(2):99–106

    Article  CAS  Google Scholar 

  • Wang Y, Cui H, Zhou J, Li F, Wang J, Chen M, Liu Q (2015) Cytotoxicity, DNA damage, and apoptosis induced by titanium dioxide nanoparticles in human non-small cell lung cancer a549 cells. Environ Sci Pollut Res Int 22(7):5519–5530

    Article  CAS  Google Scholar 

  • Wu J, Liu W, Xue C, Zhou S, Lan F, Bi L, Xu H, Yang X, Zeng F-D (2009) Toxicity and penetration of tio2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure. Toxicol Lett 191(1):1–8

    Article  CAS  Google Scholar 

  • Yeung A, Tzvetkov N, El-Tawil O, Bungǎu S, Abdel-Daim M, Atanasov A (2019) Antioxidants: scientific literature landscape analysis. Oxid Med Cell Longev, 2019

  • Ze Y, Hu R, Wang X, Sang X, Ze X, Li B, Su J, Wang Y, Guan N, Zhao X (2014a) Neurotoxicity and gene-expressed profile in brain-injured mice caused by exposure to titanium dioxide nanoparticles. J Biomed Mater Res A 102(2):470–478

    Article  Google Scholar 

  • Ze Y, Sheng L, Zhao X, Hong J, Ze X, Yu X, Pan X, Lin A, Zhao Y, Zhang C (2014b) Tio2 nanoparticles induced hippocampal neuroinflammation in mice. PloS one 9(3):e92230

    Article  Google Scholar 

Download references

Acknowledgements

This research was part of a Ph.D. thesis supported by Tehran University of Medical Sciences and Health Services (grant number 9611138001 and 99-2-99-49075). The authors are grateful to the Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, for the technical support and collaboration.

Author information

Authors and Affiliations

  1. Department of Occupational Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Peymaneh Habibi, Mohammad Reza Monazzam & Farideh Golbabaei

  2. Toxicology and Poisoning Research Centre, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Nasser Ostad

  3. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Abbas Rahimi Foroushani

  4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mahmoud Ghazi-Khansari

  5. Department of Medical Education, Virtual University of Medical Sciences, Tehran, Iran

    Shima Aliebrahimi

  6. Department of Clinical Pharmacy, Virtual University of Medical Sciences, Tehran, Iran

    Vahideh Montazeri

Authors
  1. Peymaneh Habibi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seyed Nasser Ostad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad Reza Monazzam
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abbas Rahimi Foroushani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mahmoud Ghazi-Khansari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shima Aliebrahimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vahideh Montazeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Farideh Golbabaei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.Gh.Kh. and M.R.M. conceived of the presented idea. P.H. helped in the coordination of the study and material preparation. A.R.F. performed statistical analysis and interpretation and drafted the manuscript. S.N.O. and F.G. supervised the first draft and commented on previous version of the manuscript. V.M. discussed the results and encouraged investigating a specific aspect of this work. SH.A. helped in the data collection and designed the analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Farideh Golbabaei.

Ethics declarations

Ethics approval

The thesis was approved by the Medical Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.SPH.REC.1399.044).

Consent to publication

Not applicable.

Consent to participant

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Responsible Editor: Mohamed M. Abdel-Daim

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Habibi, P., Ostad, S.N., Monazzam, M.R. et al. Thermal stress and TiO2 nanoparticle–induced oxidative DNA damage and apoptosis in mouse hippocampus. Environ Sci Pollut Res 29, 90128–90139 (2022). https://doi.org/10.1007/s11356-022-21796-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-022-21796-5

Keywords

Search

Navigation