Journal Home > Volume 14 , Issue 4
Nano Biomedicine and Engineering 2022, 14(4): 329-342 https://doi.org/10.5101/nbe.v14i4.p329-342
Review | Open Access | Issue | Published: 31 December 2022

Titanium Dioxide Nanoparticle and Cardiovascular Diseases: A Critical Review of the Literature and Possible Underlying Mechanisms

Show Author's Information Shiva Mehran1,  Soroush Ghodratizadeh2,  Ali Zolfi-Gol3,  Hamed Charkhian4,  Mojtaba Ranjbari4,  Vahed Ebrahimi5,  Zafar Gholinejad6( )
Department of Biology, Higher Education Institute of Rabe-Rashidi, Tabriz, Iran
Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
Department of Pediatrics Cardiology, Shahid Motahari Hospital, Urmia University of Medical Sciences, Urmia, Iran
Department of Biology, Urmia Branch, Islamic Azad University, Urmia, Iran
Department of Biochemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
Department of Medical Laboratory Science, Urmia Branch, Islamic Azad University, Urmia, Iran
Keywords:
Inflammation, Nanoparticle, Titanium dioxide, Oxidative stress, Cardiovascular diseases, Endothelial dysfunction, Cardiac injury
Cite this article:
Mehran S, Ghodratizadeh S, Zolfi-Gol A, et al. Titanium Dioxide Nanoparticle and Cardiovascular Diseases: A Critical Review of the Literature and Possible Underlying Mechanisms. Nano Biomedicine and Engineering, 2022, 14(4): 329-342. https://doi.org/10.5101/nbe.v14i4.p329-342
Download citation
EndNote(RIS)
BibTeX

872

Views

169

Downloads

Citations

0

Crossref

N/A

WoS

0

Scopus

N/A

CSCD

Abstract Full text About this article
Background

Over the last decades, the exposure to titanium dioxide nanoparticles (TiO2 NPs) has increased due to the wide application in industry, food adduct, medicine, cosmetic products, etc. Literature review showed that the TiO2 NPs exert toxic effects on several organs.

Methods

We searched PubMed, MEDLINE and the other databases with the following keywords, "titanium dioxide nanoparticle", "TiO2 NPs", "myocardial infarction", "endothelial", "blood pressure", "heart" and "cardiovascular", and reviewed the literature by focusing on the toxic effects of TiO2 NPs on the cardiovascular system, and possible underlying mechanism.

Results

The toxic effects of TiO2 NPs on the cardiovascular system are controversial but some possible mechanisms were proposed. TiO2 NPs and nanoparticle-derived titanium induce cardiac injury, endothelial dysfunction and increase blood pressure and heart rate. These effects are mediated via systemic or local oxidative stress and inflammation.

Conclusion

The TiO2 NPs toxicity is dependent on cell type and particle characteristic, and the controversial results may be due to these variables. However, a growing body of evidence confirmed the possible TiO2 NPs toxicity on the cardiovascular system.


menu
Abstract
Full text
Outline
About this article

Titanium Dioxide Nanoparticle and Cardiovascular Diseases: A Critical Review of the Literature and Possible Underlying Mechanisms

Show Author's information Shiva Mehran1, Soroush Ghodratizadeh2, Ali Zolfi-Gol3, Hamed Charkhian4, Mojtaba Ranjbari4, Vahed Ebrahimi5, Zafar Gholinejad6( )
Department of Biology, Higher Education Institute of Rabe-Rashidi, Tabriz, Iran
Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
Department of Pediatrics Cardiology, Shahid Motahari Hospital, Urmia University of Medical Sciences, Urmia, Iran
Department of Biology, Urmia Branch, Islamic Azad University, Urmia, Iran
Department of Biochemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
Department of Medical Laboratory Science, Urmia Branch, Islamic Azad University, Urmia, Iran

Abstract

Background

Over the last decades, the exposure to titanium dioxide nanoparticles (TiO2 NPs) has increased due to the wide application in industry, food adduct, medicine, cosmetic products, etc. Literature review showed that the TiO2 NPs exert toxic effects on several organs.

Methods

We searched PubMed, MEDLINE and the other databases with the following keywords, "titanium dioxide nanoparticle", "TiO2 NPs", "myocardial infarction", "endothelial", "blood pressure", "heart" and "cardiovascular", and reviewed the literature by focusing on the toxic effects of TiO2 NPs on the cardiovascular system, and possible underlying mechanism.

Results

The toxic effects of TiO2 NPs on the cardiovascular system are controversial but some possible mechanisms were proposed. TiO2 NPs and nanoparticle-derived titanium induce cardiac injury, endothelial dysfunction and increase blood pressure and heart rate. These effects are mediated via systemic or local oxidative stress and inflammation.

Conclusion

The TiO2 NPs toxicity is dependent on cell type and particle characteristic, and the controversial results may be due to these variables. However, a growing body of evidence confirmed the possible TiO2 NPs toxicity on the cardiovascular system.

Keywords: Inflammation, Nanoparticle, Titanium dioxide, Oxidative stress, Cardiovascular diseases, Endothelial dysfunction, Cardiac injury

References(121)

[1]

G. Santulli. Epidemiology of cardiovascular disease in the 21st century: Updated numbers and updated facts. Journal of Cardiovascular Disease Research, 2013, 1: 1.
Google Scholar
[2]

L. Dai, Y.F. Qi, L.X. Jia, et al. Nanotechnology in Cardiovascular Diseases. Encyclopedia of Nanotechnology. Dordrecht: Springer, 2015: 1‒4. https://doi.org/10.1007/978-94-007-6178-0_336-2
DOI
[3]

Z.L. Han, J.N. Shu, X. Liang, et al. Label-free ratiometric electrochemiluminescence aptasensor based on nanographene oxide wrapped titanium dioxide nanoparticles with potential-resolved electrochemilumine-scence. Analytical Chemistry, 2019, 91: 12260‒12267. https://doi.org/10.1021/acs.analchem.9b02318
DOI Google Scholar
[4]

M.P. Mani, S.K. Jaganathan, A.M. Faudzi, et al. Engineered electrospun polyurethane composite patch combined with Bi-functional components rendering high strength for cardiac tissue engineering. Polymers, 2019, 11: 705. https://doi.org/10.3390/polym11040705
DOI Google Scholar
[5]

M.P. Sauvant, D. Pepin. Drinking water and cardiovascular disease. Food and Chemical Toxicology, 2002, 40: 1311‒1325. https://doi.org/10.1016/S0278-6915(02)00081-9
DOI Google Scholar
[6]

B.A. Franklin, R. Brook, C. Arden Pope. Air pollution and cardiovascular disease. Current Problems in Cardiology, 2015, 40: 207‒238. https://doi.org/10.1016/j.cpcardiol.2015.01.003
DOI Google Scholar
[7]

A. Weir, P. Westerhoff, L. Fabricius, et al. Titanium dioxide nanoparticles in food and personal care products. Environmental Science & Technology, 2012, 46: 2242‒2250. https://doi.org/10.1021/es204168d
DOI Google Scholar
[8]

H. Kaminski, M. Beyer, H. Fissan, et al. Measurements of nanoscale TiO2 and Al2O3 in industrial workplace environments - methodology and results. Aerosol and Air Quality Research, 2015, 15: 129‒141. https://doi.org/10.4209/aaqr.2014.03.0065
DOI Google Scholar
[9]

B. Dréno, A. Alexis, B. Chuberre, et al. Safety of titanium dioxide nanoparticles in cosmetics. Journal of the European Academy of Dermatology Venereology, 2019, 33: 34‒46. https://doi.org/10.1111/jdv.15943
DOI Google Scholar
[10]

J. Musial, R. Krakowiak, D.T. Mlynarczyk, et al. Titanium dioxide nanoparticles in food and personal care products-what do we know about their safety? Nanomaterials (Basel), 2020, 10: 1110. https://doi.org/10.3390/nano10061110
DOI Google Scholar
[11]

A.B. da Silva, M. Miniter, W. Thom, et al. Gastrointestinal absorption and toxicity of nanoparticles and microparticles: Myth, reality and pitfalls explored through titanium dioxide. Current Opinion in Toxicology, 2020, 19: 112‒120. https://doi.org/10.1016/j.cotox.2020.02.007
DOI Google Scholar
[12]

Y.F. Li, J.G. Li, J.L. Yin, et al. Systematic influence induced by 3 nm titanium dioxide following intratracheal instillation of mice. Journal of Nanoscience Nanotechnology, 2010, 10: 8544‒8549. https://doi.org/10.1166/jnn.2010.2690
DOI Google Scholar
[13]

W. Sun, Y.X. Du, J.Q. Chen, et al. Interaction between titanium dioxide nanoparticles and human serum albumin revealed by fluorescence spectroscopy in the absence of photoactivation. Journal of Luminescence, 2009, 129: 778‒783. https://doi.org/10.1016/j.jlumin.2009.02.010
DOI Google Scholar
[14]

R. Tantra, J. Tompkins, P. Quincey. Characterisation of the de-agglomeration effects of bovine serum albumin on nanoparticles in aqueous suspension. Colloids and Surfaces B: Biointerfaces, 2010, 75: 275‒281. https://doi.org/10.1016/j.colsurfb.2009.08.049
DOI Google Scholar
[15]

M. Eydner, D. Schaudien, O. Creutzenberg, et al. Impacts after inhalation of nano- and fine-sized titanium dioxide particles: Morphological changes, translocation within the rat lung, and evaluation of particle deposition using the relative deposition index. Inhalation Toxicology, 2012, 24: 557‒569. https://doi.org/10.3109/08958378.2012.697494
DOI Google Scholar
[16]

W. Souza, S.G. Piperni, P. Laviola, et al. The two faces of titanium dioxide nanoparticles bio-camouflage in 3D bone spheroids. Scientific Reports, 2019, 9: 9309. https://doi.org/10.1038/s41598-019-45797-6
DOI Google Scholar
[17]

M. Skocaj, M. Filipic, J. Petkovic, et al. Titanium dioxide in our everyday life; is it safe? Radiology and Oncology, 2011, 45: 227‒247. https://doi.org/10.2478/v10019-011-0037-0
DOI Google Scholar
[18]

M. Benčina, A. Iglič, M. Mozetič, et al. Crystallized TiO2 nanosurfaces in biomedical applications. Nanomaterials (Basel), 2020, 10: 1121. https://doi.org/10.3390/nano10061121
DOI Google Scholar
[19]

19. T. Kodama. Study on biocompatibility of titanium alloys. Kokubyo Gakkai Zasshi, 1989, 56: 263‒288. https://doi.org/10.5357/koubyou.56.263
DOI Google Scholar
[20]

E. Le Roux. Recent advances on tailor-made titanium catalysts for biopolymer synthesis. Coordination Chemistry Reviews, 2016, 306: 65‒85. https://doi.org/10.1016/j.ccr.2015.06.006
DOI Google Scholar
[21]

H.B. Shi, R. Magaye, V. Castranova, et al. Titanium dioxide nanoparticles: A review of current toxicological data. Particle and Fibre Toxicology, 2013, 10: 15. https://doi.org/10.1186/1743-8977-10-15
DOI Google Scholar
[22]

I. Iavicoli, V. Leso, A. Bergamaschi. Toxicological effects of titanium dioxide nanoparticles: A review of in vivo studies. Journal of Nanomaterials, 2012, 2012: 5. https://doi.org/10.1155/2012/964381
DOI Google Scholar
[23]

I. Iavicoli, V. Leso, L. Fontana, et al. Toxicological effects of titanium dioxide nanoparticles: A review of in vitro mammalian studies. European Review for Medical and Pharmacological Sciences, 2011, 15: 481‒508.
Google Scholar
[24]

R.D. Handy, B.J. Shaw. Toxic effects of nanoparticles and nanomaterials: Implications for public health, risk assessment and the public perception of nanotechnology. Health, Risk & Society, 2007, 9: 125‒144. https://doi.org/10.1080/13698570701306807
DOI Google Scholar
[25]

J.X. Wang, Y.B. Fan. Lung injury induced by TiO2 nanoparticles depends on their structural features: Size, shape, crystal phases, and surface coating. International Journal of Molecular Sciences, 2014, 15: 22258‒22278. https://doi.org/10.3390/ijms151222258
DOI Google Scholar
[26]

J.K. Jiang, G. Oberdörster, P. Biswas. Characterization of size, surface charge, and agglomeration state of nanoparticle dispersions for toxicological studies. Journal of Nanoparticle Research, 2009, 11: 77‒89. https://doi.org/10.1007/s11051-008-9446-4
DOI Google Scholar
[27]

M. Shakeel, F. Jabeen, S. Shabbir, et al. Toxicity of nano-titanium dioxide (TiO2-NP) through various routes of exposure: A review. Biological Trace Element Research, 2016, 172: 1‒36. https://doi.org/10.1007/s12011-015-0550-x
DOI Google Scholar
[28]

B. Uttara, A.V. Singh, P. Zamboni, et al. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Current neuropharmacology, 2009, 7: 65‒74. https://doi.org/10.2174/157015909787602823
DOI Google Scholar
[29]

D.A. Pratt, K.A. Tallman, N.A. Porter. Free radical oxidation of polyunsaturated lipids: New mechanistic insights and the development of peroxyl radical clocks. Accounts of chemical Research, 2011, 44: 458‒467. https://doi.org/10.1021/ar200024c
DOI Google Scholar
[30]

J. Hou, L.Y. Wang, C.J. Wang, et al. Toxicity and mechanisms of action of titanium dioxide nanoparticles in living organisms. Journal of Environmental Sciences, 2019, 75: 40‒53. https://doi.org/10.1016/j.jes.2018.06.010
DOI Google Scholar
[31]

S.H. Lee, S.K. Jeong, S.K. Ahn. An update of the defensive barrier function of skin. Yonsei Medical Journal, 2006, 47: 293‒306. https://doi.org/10.3349/ymj.2006.47.3.293
DOI Google Scholar
[32]

R.E. Baynes, E. Hodgson. Absorption and distribution of toxicants. A Textbook of Modern Toxicology. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2004: 75‒110. https://doi.org/10.1002/0471646776.ch6
DOI Google Scholar
[33]

E. Huerta-García, M.P. Ramos-Godinez, A. López-Saavedra, et al. Internalization of titanium dioxide nanoparticles is mediated by actin-dependent reorganization and clathrin- and dynamin-mediated endocytosis in H9C2 rat cardiomyoblasts. Chemical Research in Toxicology, 2019, 32: 578‒588. https://doi.org/10.1021/acs.chemrestox.8b00284
DOI Google Scholar
[34]

L. Sheng, X.C. Wang, X.Z. Sang, et al. Cardiac oxidative damage in mice following exposure to nanoparticulate titanium dioxide. Journal of Biomedical Materials Research Part A, 2013, 101: 3238‒3246. https://doi.org/10.1002/jbm.a.34634
DOI Google Scholar
[35]

M. Savi, S. Rossi, L. Bocchi, et al. Titanium dioxide nanoparticles promote arrhythmias via a direct interaction with rat cardiac tissue. Particle and Fibre Toxicology, 2014, 11: 63. https://doi.org/10.1186/s12989-014-0063-3
DOI Google Scholar
[36]

H. Kan, Z.X. Wu, S.H. Young, et al. Pulmonary exposure of rats to ultrafine titanium dioxide enhances cardiac protein phosphorylation and substance P synthesis in nodose Ganglia. Nanotoxicology, 2012, 6: 736‒745. https://doi.org/10.3109/17435390.2011.611915
DOI Google Scholar
[37]

X.H. Chang, Y.X. Xie, J.R. Wu, et al. Toxicological characteristics of titanium dioxide nanoparticle in rats. Journal of Nanoscience and Nanotechnology, 2015, 15: 1135-1142. https://doi.org/10.1166/jnn.2015.8998
DOI Google Scholar
[38]

J.X. Wang, G.Q. Zhou, C.Y. Chen, et al. Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicology Letters, 2007, 168: 176‒185. https://doi.org/10.1016/j.toxlet.2006.12.001
DOI Google Scholar
[39]

A. Nemmar, K. Melghit, B.H. Ali. The acute proinflammatory and prothrombotic effects of pulmonary exposure to rutile TiO2 nanorods in rats. Experimental Biology and Medicine, 2008, 233: 610‒619. https://doi.org/10.3181/0706-rm-165
DOI Google Scholar
[40]

F.S. Hong, L. Wang, X.H. Yu, et al. Toxicological effect of TiO2 nanoparticle-induced myocarditis in mice. Nanoscale Research Letters, 2015, 10: 326. https://doi.org/10.1186/s11671-015-1029-6
DOI Google Scholar
[41]

H.T. Liu, L.L. Ma, J.F. Zhao, et al. Biochemical toxicity of nano-anatase TiO2 particles in mice. Biological Trace Element Research, 2009, 129: 170‒180. https://doi.org/10.1007/s12011-008-8285-6
DOI Google Scholar
[42]

J.Y. Chen, X. Dong, J. Zhao, et al. In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection. Journal of Applied Toxicology, 2009, 29: 330‒337. https://doi.org/10.1002/jat.1414
DOI Google Scholar
[43]

D. Elgrabli, R. Beaudouin, N. Jbilou, et al. Biodistribution and clearance of TiO2 nanoparticles in rats after intravenous injection. PLoS One, 2015, 10: e0124490. https://doi.org/10.1371/journal.pone.0124490
DOI Google Scholar
[44]

Y. Wang, Z.J. Chen, T. Ba, et al. Susceptibility of young and adult rats to the oral toxicity of titanium dioxide nanoparticles. Small, 2013, 9: 1742‒1752. https://doi.org/10.1002/smll.201201185
DOI Google Scholar
[45]

Z.J. Chen, Y. Wang, L. Zhuo, et al. Effect of titanium dioxide nanoparticles on the cardiovascular system after oral administration. Toxicology Letters, 2015, 239: 123‒130. https://doi.org/10.1016/j.toxlet.2015.09.013
DOI Google Scholar
[46]

X.H. Yu, X.Y. Zhao, Y.G. Ze, et al. Changes of serum parameters of TiO2 nanoparticle-induced atherosclerosis in mice. Journal of Hazardous Materials, 2014, 280: 364‒371. https://doi.org/10.1016/j.jhazmat.2014.08.015
DOI Google Scholar
[47]

T. Chen, J.Q. Hu, C.Y. Chen, et al. Cardiovascular effects of pulmonary exposure to titanium dioxide nanoparticles in ApoE knockout mice. Journal of Nanoscience and Nanotechnology, 2013, 13: 3214-3222. https://doi.org/10.1166/jnn.2013.7147
DOI Google Scholar
[48]

L. Mikkelsen, M. Sheykhzade, K.A. Jensen, et al. Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO(2). Particle and Fibre Toxicology, 2011, 8: 32. https://doi.org/10.1186/1743-8977-8-32
DOI Google Scholar
[49]

J.Q. Hu, C.Y. Chen, R. Bai, et al. Effect of nano-TiO(2) intratracheal instillation on lipid metabolism of AopE gene-knockout mice. Zhonghua Yu Fang Yi Xue Za Zhi Chinese Journal of Preventive Medicine, 2010, 44: 780‒784. https://doi.org/10.3760/CMA.J.ISSN.0253-9624.2010.09.004
DOI Google Scholar
[50]

M. Tang, T. Zhang, Y.Y. Xue, et al. Metabonomic studies of biochemical changes in the serum of rats by intratracheally instilled TiO2 nanoparticles. Journal of Nanoscience and Nanotechnology, 2011, 11: 3065‒3074. https://doi.org/10.1166/jnn.2011.3604
DOI Google Scholar
[51]

H.L. Hu, Q. Guo, C.L. Wang, et al. Titanium dioxide nanoparticles increase plasma glucose via reactive oxygen species-induced insulin resistance in mice. Journal of Applied Toxicology, 2015, 35: 1122‒1132. https://doi.org/10.1002/jat.3150
DOI Google Scholar
[52]

Z.J. Chen, D. Zhou, Y. Wang, et al. Combined effect of titanium dioxide nanoparticles and glucose on the cardiovascular system in young rats after oral administration. Journal of Appllied Toxicology, 2019, 39: 590‒602. https://doi.org/10.1002/jat.3750
DOI Google Scholar
[53]

Y. Suzuki, S. Tada-Oikawa, G. Ichihara, et al. Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation. Toxicology and Applied Pharmacology, 2014, 278: 16‒25. https://doi.org/10.1016/j.taap.2014.04.010
DOI Google Scholar
[54]

M. Giovanni, J. Yue, L. Zhang, et al. Pro-inflammatory responses of RAW264.7 macrophages when treated with ultralow concentrations of silver, titanium dioxide, and zinc oxide nanoparticles. Journal of Hazardous Materials, 2015, 297: 146‒152. https://doi.org/10.1016/j.jhazmat.2015.04.081
DOI Google Scholar
[55]

S. Triboulet, C. Aude-Garcia, L. Armand, et al. Comparative proteomic analysis of the molecular responses of mouse macrophages to titanium dioxide and copper oxide nanoparticles unravels some toxic mechanisms for copper oxide nanoparticles in macro-phages. PLoS One, 2015, 10: e0124496. https://doi.org/10.1371/journal.pone.0124496
DOI Google Scholar
[56]

R. Liu, X.Y. Zhang, Y.P. Pu, et al. Small-sized titanium dioxide nanoparticles mediate immune toxicity in rat pulmonary alveolar macrophages in vivo. Journal of Nanoscience and Nanotechnology, 2010, 10: 5161‒5169. https://doi.org/10.1166/jnn.2010.2420
DOI Google Scholar
[57]

W.C. Xu, X. Dong, J.L. Ding, et al. Nanotubular TiO2 regulates macrophage M2 polarization and increases macrophage secretion of VEGF to accelerate endothelialization via the ERK1/2 and PI3K/AKT pathways. International Journal of Nanomedicine, 2019, 14: 441‒455. https://doi.org/10.2147/ijn.s188439
DOI Google Scholar
[58]

Y. Hou, M. Lai, X. Chen, et al. Effects of mesoporous SiO2, Fe3O4, and TiO2 nanoparticles on the biological functions of endothelial cells in vitro. Journal of Biomedical Materials Research Part A, 2014, 102: 1726‒1736. https://doi.org/10.1002/jbm.a.34839
DOI Google Scholar
[59]

Z. Gholinejad, A. Ghasemian, Y. Tutar, et al. N-acetyl cysteine and metal nanoparticles internalization: A critical methodological aspect. Journal of Bionanoscience, 2018, 12: 700‒704. https://doi.org/10.1166/jbns.2018.1587
DOI Google Scholar
[60]

E. Huerta-García, J.A. Pérez-Arizti, S.G. Márquez-Ramírez, et al. Titanium dioxide nanoparticles induce strong oxidative stress and mitochondrial damage in glial cells. Free Radical Biology and Medicine, 2014, 73: 84‒94. https://doi.org/10.1016/j.freeradbiomed.2014.04.026
DOI Google Scholar
[61]

A. Montiel-Dávalos, J.L. Ventura-Gallegos, E. Alfaro-Moreno, et al. TiO2 nanoparticles induce dysfunction and activation of human endothelial cells. Chemical Research in Toxicology, 2012, 25: 920‒930. https://doi.org/10.1021/tx200551u
DOI Google Scholar
[62]

M.D.E.L.P. Ramos-Godínez, B.E. González-Gómez, A. Montiel-Dávalos, et al. TiO2 nanoparticles induce endothelial cell activation in a pneumocyte-endothelial co-culture model. Toxicology in Vitro Int. J. Publ. Assoc. BIBRA, 2013, 27: 774‒781. https://doi.org/10.1016/j.tiv.2012.12.010
DOI Google Scholar
[63]

S.G. Han, B. Newsome, B. Hennig. Titanium dioxide nanoparticles increase inflammatory responses in vascular endothelial cells. Toxicology, 2013, 306: 1‒8. https://doi.org/10.1016/j.tox.2013.01.014
DOI Google Scholar
[64]

S. Guney-Ayra, et al. Induction of oxidative stress, lysosome activation and autophagy by nanoparticles in human brain-derived endothelial cells. Biochemical Journal, 2012, 441: 813‒821. https://doi.org/10.1042/bj20111252
DOI Google Scholar
[65]

R. Alinovi, M. Goldoni, S. Pinelli, et al. Oxidative and pro-inflammatory effects of cobalt and titanium oxide nanoparticles on aortic and venous endothelial cells. Toxicology in Vitro, 2015, 29: 426‒437. https://doi.org/10.1016/j.tiv.2014.12.007
DOI Google Scholar
[66]

Z. Gholinejad, M.H. Khadem Ansari, Y. Rasmi. Titanium dioxide nanoparticles induce endothelial cell apoptosis via cell membrane oxidative damage and p38, PI3K/Akt, NF-κB signaling pathways modulation. Journal of Trace Elements in Medicine and Biology, 2019, 54: 27‒35. https://doi.org/10.1016/j.jtemb.2019.03.008
DOI Google Scholar
[67]

Q.A. Hathaway, A.J. Durr, D.L. Shepherd, et al. miRNA-378a as a key regulator of cardiovascular health following engineered nanomaterial inhalation exposure. Nanotoxicology, 2019, 13: 644‒663. https://doi.org/10.1080/17435390.2019.1570372
DOI Google Scholar
[68]

Q.Q. Yan, L. Yang, J. Zhao, et al. Comparative experiment on nanoparticle-induced toxicity in human vascular endothelial cells. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, Chinese Journal of Industrial Hygiene and Occupational Diseases 2012, 30: 820‒824.
Google Scholar
[69]

L. Peng, A.J. Barczak, R.A. Barbeau, et al. Whole genome expression analysis reveals differential effects of TiO2 nanotubes on vascular cells. Nano Letters, 2010, 10: 143‒148. https://doi.org/10.1021/nl903043z
DOI Google Scholar
[70]

Y.X. Gu, S.S. Cheng, G. Chen, et al. The effects of endoplasmic reticulum stress inducer thapsigargin on the toxicity of ZnO or TiO2 nanoparticles to human endothelial cells. Toxicology Mechanisms and Methods, 2017, 27: 191‒200. https://doi.org/10.1080/15376516.2016.1273429
DOI Google Scholar
[71]

N. Bayat, V.R. Lopes, J. Schölermann, et al. Vascular toxicity of ultra-small TiO2 nanoparticles and single walled carbon nanotubes in vitro and in vivo. Biomaterials, 2015, 63: 1‒13. https://doi.org/10.1016/j.biomaterials.2015.05.044
DOI Google Scholar
[72]

V. Spigoni, M. Cito, R. Alinovi, et al. Effects of TiO2 and Co3O4 nanoparticles on circulating angiogenic cells. PLoS One, 2015, 10: e0119310. https://doi.org/10.1371/journal.pone.0119310
DOI Google Scholar
[73]

S. Smulders, K. Luyts, G. Brabants, et al. Toxicity of nanoparticles embedded in paints compared to pristine nanoparticles, in vitro study. Toxicology Letters, 2015, 232: 333‒339. https://doi.org/10.1016/j.toxlet.2014.11.030
DOI Google Scholar
[74]

R. Bengalli, P. Mantecca, M. Camatini, et al. Effect of nanoparticles and environmental particles on a cocultures model of the air-blood barrier. Biomed Res. Int. , 2013, 2013: 801214. https://doi.org/10.1155/2013/801214
DOI Google Scholar
[75]

T.R. Nurkiewicz, D.W. Porter, A.F. Hubbs, et al. Pulmonary particulate matter and systemic microvascular dysfunction. Research report (Health Effects Institute), 2011: 3‒48.
Google Scholar
[76]

T.R. Nurkiewicz, D.W. Porter, A.F. Hubbs, et al. Pulmonary nanoparticle exposure disrupts systemic microvascular nitric oxide signaling. Toxicological Science, 2009, 110: 191‒203. https://doi.org/10.1093/toxsci/kfp051
DOI Google Scholar
[77]

A. Courtois, P. Andujar, Y. Ladeiro, et al. Impairment of NO-dependent relaxation in intralobar pulmonary arteries: Comparison of urban particulate matter and manufactured nanoparticles. Environmental Health Perspectives, 2008, 116: 1294‒1299. https://doi.org/10.1289/ehp.11021
DOI Google Scholar
[78]

M.I. Setyawati, C.Y. Tay, S.L. Chia, et al. Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin. Nature Communications, 2013, 4: 1673. https://doi.org/10.1038/ncomms2655
DOI Google Scholar
[79]

W.I. Hagens, A.G. Oomen, W.H. de Jong, et al. What do we (need to) know about the kinetic properties of nanoparticles in the body? Regulatory Toxicology and Pharmacology, 2007, 49: 217‒229. https://doi.org/10.1016/j.yrtph.2007.07.006
DOI Google Scholar
[80]

Y.M. Duan, J. Liu, L.L. Ma, et al. Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice. Biomaterials, 2010, 31: 894‒899. https://doi.org/10.1016/j.biomaterials.2009.10.003
DOI Google Scholar
[81]

D. Vasantharaja, V. Ramalingam, G. Reddy. Titanium dioxide nanoparticles induced alteration in haematological indices of adult male wistar rats. Journal of Academia and Industrial Research, 2015.3: 632‒635.
Google Scholar
[82]

X.Z. Sang, L. Zheng, Q.Q. Sun, et al. The chronic spleen injury of mice following long-term exposure to titanium dioxide nanoparticles. Journal of Biomedical Materials Research Part A, 2012, 100A: 894‒902. https://doi.org/10.1002/jbm.a.34024
DOI Google Scholar
[83]

M. Ghosh, A. Chakraborty, A. Mukherjee. Cytotoxic, genotoxic and the hemolytic effect of titanium dioxide (TiO2) nanoparticles on human erythrocyte and lymphocyte cells in vitro. Journal of Applied Toxicology, 2013, 33: 1097‒1110. https://doi.org/10.1002/jat.2863
DOI Google Scholar
[84]

I. Grissa, J. Elghoul, L. Ezzi, et al. Anemia and genotoxicity induced by sub-chronic intragastric treatment of rats with titanium dioxide nanoparticles. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2015, 794: 25‒31. https://doi.org/10.1016/j.mrgentox.2015.09.005
DOI Google Scholar
[85]

N. Haberl, S. Hirn, M. Holzer, et al. Effects of acute systemic administration of TiO2, ZnO, SiO2, and Ag nanoparticles on hemodynamics, hemostasis and leukocyte recruitment. Nanotoxicology, 2015, 9: 963‒971. https://doi.org/10.3109/17435390.2014.992815
DOI Google Scholar
[86]

J.Y. Xu, H.B. Shi, M. Ruth, et al. Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice. PLoS One, 2013, 8: e70618. https://doi.org/10.1371/journal.pone.0070618
DOI Google Scholar
[87]

N.R. Ben Younes, S. Amara, I. Mrad, et al. Subacute toxicity of titanium dioxide (TiO2) nanoparticles in male rats: Emotional behavior and pathophysiological examination. Environmental Science and Pollution Research, 2015, 22: 8728‒8737. https://doi.org/10.1007/s11356-014-4002-5
DOI Google Scholar
[88]

Z.J. Deng, G. Mortimer, T. Schiller, et al. Differential plasma protein binding to metal oxide nanoparticles. Nanotechnology, 2009, 20: 455101. https://doi.org/10.1088/0957-4484/20/45/455101
DOI Google Scholar
[89]

B. Ekstrand-Hammarström, J. Hong, P. Davoodpour, et al. TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations. Biomaterials, 2015, 51: 58‒68. https://doi.org/10.1016/j.biomaterials.2015.01.031
DOI Google Scholar
[90]

S.C. Roy, M. Paulose, C.A. Grimes. The effect of TiO2 nanotubes in the enhancement of blood clotting for the control of hemorrhage. Biomaterials, 2007, 28: 4667‒4672. https://doi.org/10.1016/j.biomaterials.2007.07.045
DOI Google Scholar
[91]

B.M. Rothen-Rutishauser, S. Schürch, B. Haenni, et al. Interaction of fine particles and nanoparticles with red blood cells visualized with advanced microscopic techniques. Environmental Science & Technology, 2006, 40: 4353‒4359. https://doi.org/10.1021/es0522635
DOI Google Scholar
[92]

Y. Aisaka, R. Kawaguchi, S. Watanabe, et al. Hemolysis caused by titanium dioxide particles. Inhalation Toxicology, 2008, 20: 891‒893. https://doi.org/10.1080/08958370802304123
DOI Google Scholar
[93]

N.N. Zhou, X.B. Lin, D.G. Liu, et al. Efficacy and toxicity of trastuzumab combined with docetaxel for Her-2/neu overexpressing metastatic breast cancer. Chinese Journal of Cancer, 2008, 27: 947‒950.
Google Scholar
[94]

M. Entezari, F. Ghanbary. Toxicity of Manganese titanate on rat vital organ mitochondria. Iranian Journal of Pharmaceutical Research, 2019, 18: 713‒719. https://doi.org/10.22037/ijpr.2019.1100639
DOI Google Scholar
[95]

M.J.D. Clift, P. Gehr, B. Rothen-Rutishauser. Nanotoxicology: A perspective and discussion of whether or not in vitro testing is a valid alternative. Archives of Toxicology, 2011, 85: 723‒731. https://doi.org/10.1007/s00204-010-0560-6
DOI Google Scholar
[96]

C. Relier, M. Dubreuil, O. Lozano Garcia, et al. Study of TiO2 P25 nanoparticles genotoxicity on lung, blood, and liver cells in lung overload and non-overload conditions after repeated respiratory exposure in rats. Toxicological Sciences, 2017, 156: 527‒537. https://doi.org/10.1093/toxsci/kfx006
DOI Google Scholar
[97]

P.R. Forfia, A. Vaidya, S.E. Wiegers. Pulmonary heart disease: The heart-lung interaction and its impact on patient phenotypes. Pulmonary Circulation, 2013, 3: 5‒19. https://doi.org/10.4103/2045-8932.109910
DOI Google Scholar
[98]

J. Wright, A. Hutchison. Cardiovascular disease in patients with chronic kidney disease. Vascular Health and Risk Management, 2009, 5: 713‒722. https://doi.org/10.2147/vhrm.s6206
DOI Google Scholar
[99]

G. Fede, G. Privitera, T. Tomaselli, et al. Cardiovascular dysfunction in patients with liver cirrhosis. Annals of Gastroenterology, 2015, 28: 31‒40.
Google Scholar
[100]

Y. Morimoto, H. Izumi, E. Kuroda. Significance of persistent inflammation in respiratory disorders induced by nanoparticles. Journal of Immunology Research, 2014. https://doi.org/10.1155/2014/962871
DOI Google Scholar
[101]

S.X. Gui, B.Y. Li, X.Y. Zhao, et al. Renal injury and Nrf2 modulation in mouse kidney following chronic exposure to TiO2 nanoparticles. Journal of Agricultural and Food Chemistry, 2013, 61: 8959‒8968. https://doi.org/10.1021/jf402387e
DOI Google Scholar
[102]

Y.L. Cui, H.T. Liu, M. Zhou, et al. Signaling pathway of inflammatory responses in the mouse liver caused by TiO2 nanoparticles. Journal of Biomedical Materials Research Part A, 2011, 96: 221‒229. https://doi.org/10.1002/jbm.a.32976
DOI Google Scholar
[103]

P.H. Danielsen, Y. Cao, M. Roursgaard, et al. Endothelial cell activation, oxidative stress and inflammation induced by a panel of metal-based nanomaterials. Nanotoxicology, 2015, 9: 813‒824. https://doi.org/10.3109/17435390.2014.980449
DOI Google Scholar
[104]

K.M.A. Hassanein, Y.O. El-Amir. Protective effects of thymoquinone and avenanthramides on titanium dioxide nanoparticles induced toxicity in Sprague-Dawley rats. Pathology-Research and Practice, 2017, 213: 13‒22. https://doi.org/10.1016/j.prp.2016.08.002
DOI Google Scholar
[105]

B.Y. Sha, W. Gao, S.Q. Wang, et al. Nano-titanium dioxide induced cardiac injury in rat under oxidative stress. Food and Chemical Toxicology, 2013, 58: 280‒ 288. https://doi.org/10.1016/j.fct.2013.04.050
DOI Google Scholar
[106]

C.E. Nichols, D.L. Shepherd, Q.A. Hathaway, et al. Reactive oxygen species damage drives cardiac and mitochondrial dysfunction following acute nano-titanium dioxide inhalation exposure. Nanotoxicology, 2018, 12: 32‒48. https://doi.org/10.1080/17435390.2017.1416202
DOI Google Scholar
[107]

E. Huerta-García, I. Zepeda-Quiroz, H. Sánchez-Barrera, et al. Internalization of titanium dioxide nanoparticles is cytotoxic for H9C2 rat cardiomyoblasts. Molecules, 2018, 23: 1955. https://doi.org/10.3390/molecules23081955
DOI Google Scholar
[108]

E.A. El-Din, H.E. Mostafa, M.A. Samak, et al. Could curcumin ameliorate titanium dioxide nanoparticles effect on the heart? A histopathological, immunohistochemical, and genotoxic study. Environmental Science and Pollution Research, 2019, 26: 21556‒21564. https://doi.org/10.1007/s11356-019-05433-2
DOI Google Scholar
[109]

M. Hanot-Roy, E. Tubeuf, A. Guilbert, et al. Oxidative stress pathways involved in cytotoxicity and genotoxicity of titanium dioxide (TiO2) nanoparticles on cells constitutive of alveolo-capillary barrier in vitro. Toxicology in Vitro, 2016, 33: 125‒135. https://doi.org/10.1016/j.tiv.2016.01.013
DOI Google Scholar
[110]

X.H. Yu, F.S. Hong, Y.Q. Zhang. Cardiac inflammation involving in PKCε or ERK1/2-activated NF-κB signalling pathway in mice following exposure to titanium dioxide nanoparticles. Journal of Hazardous Materials, 2016, 313: 68‒77. https://doi.org/10.1016/j.jhazmat.2016.03.088
DOI Google Scholar
[111]

M. Husain, D.M. Wu, A.T. Saber, et al. Intratracheally instilled titanium dioxide nanoparticles translocate to heart and liver and activate complement cascade in the heart of C57BL/6 mice. Nanotoxicology, 2015, 9: 1013‒1022. https://doi.org/10.3109/17435390.2014.996192
DOI Google Scholar
[112]

F.S. Hong, N. Wu, X.Y. Zhao, et al. Titanium dioxide nanoparticle-induced dysfunction of cardiac hemodynamics is involved in cardiac inflammation in mice. Journal of Biomedical Materials Research Part A, 2016, 104: 2917‒2927. https://doi.org/10.1002/jbm.a.35831
DOI Google Scholar
[113]

A.J. LeBlanc, A.M. Moseley, B.T. Chen, et al. Nanoparticle inhalation impairs coronary microvascular reactivity via a local reactive oxygen species-dependent mechanism. Cardiovascular Toxicology, 2010, 10: 27‒36. https://doi.org/10.1007/s12012-009-9060-4
DOI Google Scholar
[114]

P.A. Stapleton, C.E. Nichols, J.H. Yi, et al. Microvascular and mitochondrial dysfunction in the female F1 generation after gestational TiO2 nanoparticle exposure. Nanotoxicology, 2015, 9: 941‒951. https://doi.org/10.3109/17435390.2014.984251
DOI Google Scholar
[115]

A. Kunovac, Q.A. Hathaway, M.V. Pinti, et al. ROS promote epigenetic remodeling and cardiac dysfunction in offspring following maternal engineered nanomaterial (ENM) exposure. Particle and Fibre Toxicology, 2019, 16: 24. https://doi.org/10.1186/s12989-019-0310-8
DOI Google Scholar
[116]

S. Ichihara, W.H. Li, S. Omura, et al. Exposure assessment and heart rate variability monitoring in workers handling titanium dioxide particles: A pilot study. Journal of Nanoparticle Research, 2016, 18: 52. https://doi.org/10.1007/s11051-016-3340-2
DOI Google Scholar
[117]

S. Rossi, M. Savi, M. Mazzola, et al. Subchronic exposure to titanium dioxide nanoparticles modifies cardiac structure and performance in spontaneously hypertensive rats. Particle and Fibre Toxicology, 2019, 16: 25. https://doi.org/10.1186/s12989-019-0311-7
DOI Google Scholar
[118]

W. Chung, J. Song, J. Lee. The evaluation of titanium dioxide nanoparticle effects on cardiac and swimming performance of Daphnia magna. International Journal of Applied Environmental Sciences, 2016. 11(6): 1375‒1385.
Google Scholar
[119]

B. Song, J. Liu, X.L. Feng, et al. A review on potential neurotoxicity of titanium dioxide nanoparticles. Nanoscale Research Letters, 2015, 10: 1042. https://doi.org/10.1186/s11671-015-1042-9
DOI Google Scholar
[120]

P.J. Winklewski, M. Radkowski, M. Wszedybyl-Winklewska, et al. Brain inflammation and hypertension: The chicken or the egg? Journal of Neuroinflammation, 2015, 12: 85. https://doi.org/10.1186/s12974-015-0306-8
DOI Google Scholar
[121]

I.A. Mudunkotuwa, T.R. Anthony, V.H. Grassian, et al. Accurate quantification of TiO2 nanoparticles collected on air filters using a microwave-assisted acid digestion method. Journal of Occupational and Environmental Hygiene, 2016, 13: 30‒39. https://doi.org/10.1080/15459624.2015.1072278
DOI Google Scholar
Publication history
Copyright
Rights and permissions

Publication history

Received: 13 July 2022
Revised: 03 November 2022
Accepted: 28 November 2022
Published: 31 December 2022
Issue date: December 2022

Copyright

© Shiva Mehran, Soroush Ghodratizadeh, Ali Zolfi-Gol, Hamed Charkhian, Mojtaba Ranjbari, Vahed ebrahimi and Zafar Gholinejad.

Rights and permissions

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Return