Abstract
The effect of nanotitanium dioxide (TiO2-NP) in human monocytes is still unknown. Therefore, an understanding of probable cytotoxicity of TiO2-NP on human monocytes and underlining the mechanisms involved is of significant interest. The aim of this study was to assess the cytotoxicity of TiO2-NP on human monocytes. Using biochemical and flow cytometry assessments, we demonstrated that addition of TiO2-NP at 10 μg/ml concentration to monocytes induced cytotoxicity following 12 h. The TiO2-NP-induced cytotoxicity on monocytes was associated with intracellular reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) collapse, lysosomal membrane injury, lipid peroxidation, and depletion of glutathione. According to our results, TiO2-NP triggers oxidative stress and organelles damages in monocytes which are important cells in defense against foreign agents. Finally, our findings suggest that use of antioxidants and mitochondrial/lysosomal protective agents could be of benefit for the people in the exposure with TiO2-NP.
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References
Böhme S, Stärk H-J, Meißner T, Springer A, Reemtsma T, Kühnel D, Busch W (2014) Quantification of Al2O3 nanoparticles in human cell lines applying inductively coupled plasma mass spectrometry (neb-ICP-MS, LA-ICP-MS) and flow cytometry-based methods. J Nanopart Res 16(9):2592. https://doi.org/10.1007/s11051-014-2592-y
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72(1-2):248–254. https://doi.org/10.1016/0003-2697(76)90527-3
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. https://doi.org/10.1016/j.jhazmat.2010.07.109
Davignon J-L, Hayder M, Baron M, Boyer J-F, Constantin A, Apparailly F, Poupot R, Cantagrel A (2012) Targeting monocytes/macrophages in the treatment of rheumatoid arthritis. Rheumatology 52:590–598
Gheshlaghi ZN, Riazi GH, Ahmadian S, Ghafari M, Mahinpour R (2008) Toxicity and interaction of titanium dioxide nanoparticles with microtubule protein. Acta Biochim Biophys Sin 40(9):777–782. https://doi.org/10.1093/abbs/40.9.777
Ghosh M, Bandyopadhyay M, Mukherjee A (2010) Genotoxicity of titanium dioxide (TiO2) nanoparticles at two trophic levels: plant and human lymphocytes. Chemosphere 81(10):1253–1262. https://doi.org/10.1016/j.chemosphere.2010.09.022
Ghosh M, Chakraborty A, Mukherjee A (2013) Cytotoxic, genotoxic and the hemolytic effect of titanium dioxide (TiO2) nanoparticles on human erythrocyte and lymphocyte cells in vitro. J Appl Toxicol 33(10):1097–1110. https://doi.org/10.1002/jat.2863
Hanot-Roy M, Tubeuf E, Guilbert A, Bado-Nilles A, Vigneron P, Trouiller B, Braun A, Lacroix G (2016) Oxidative stress pathways involved in cytotoxicity and genotoxicity of titanium dioxide (TiO2) nanoparticles on cells constitutive of alveolo-capillary barrier in vitro. Toxicol in Vitro 33:125–135. https://doi.org/10.1016/j.tiv.2016.01.013
He Y-Y, Huang J-L, Block ML, Hong J-S, Chignell CF (2005) Role of phagocyte oxidase in UVA-induced oxidative stress and apoptosis in keratinocytes. J Investig Dermatol 125(3):560–566. https://doi.org/10.1111/j.0022-202X.2005.23851.x
Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74(1):214–226. https://doi.org/10.1016/0003-2697(76)90326-2
Hong J, Zhang Y-Q (2016) Murine liver damage caused by exposure to nano-titanium dioxide. Nanotechnology 27(11):112001. https://doi.org/10.1088/0957-4484/27/11/112001
Hosseini M-J, Shaki F, Ghazi-Khansari M, Pourahmad J (2013) Toxicity of vanadium on isolated rat liver mitochondria: a new mechanistic approach. Metallomics 5(2):152–166. https://doi.org/10.1039/c2mt20198d
Hussain S, Thomassen LC, Ferecatu I, Borot M-C, Andreau K, Martens JA, Fleury J, Baeza-Squiban A, Marano F, Boland S (2010) Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells. Part Fibre Toxicol 7:1
Jin C-Y, Zhu B-S, Wang X-F, Lu Q-H (2008) Cytotoxicity of titanium dioxide nanoparticles in mouse fibroblast cells. Chem Res Toxicol 21(9):1871–1877. https://doi.org/10.1021/tx800179f
Lai JC, Lai MB, Jandhyam S, Dukhande VV, Bhushan A, Daniels CK, Leung SW (2008) Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts. Int J Nanomedicine 2008:533
Li Y, Lee PY, Reeves WH (2010) Monocyte and macrophage abnormalities in systemic lupus erythematosus. Arch Immunol Ther Exp 58(5):355–364. https://doi.org/10.1007/s00005-010-0093-y
Liu H, Ma L, Liu J, Zhao J, Yan J, Hong F (2010) Toxicity of nano-anatase TiO2 to mice: liver injury, oxidative stress. Toxicol Environ Chem 92(1):175–186. https://doi.org/10.1080/02772240902732530
Long TC, Tajuba J, Sama P, Saleh N, Swartz C, Parker J, Hester S, Lowry GV, Veronesi B (2007) Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons in vitro. Environ Health Perspect 115(11):1631–1637. https://doi.org/10.1289/ehp.10216
Natarajan V, Wilson CL, Hayward SL, Kidambi S (2015) Titanium dioxide nanoparticles trigger loss of function and perturbation of mitochondrial dynamics in primary hepatocytes. PLoS One 10(8):e0134541. https://doi.org/10.1371/journal.pone.0134541
Razzaghi-Asl N, Seydi E, Alikhani R, Rezvani S, Miri R, Salimi A (2017) Synthesis and toxicity assessment of 3-oxobutanamides against human lymphocytes and isolated mitochondria. Environ Toxicol Pharmacol 51:71–84. https://doi.org/10.1016/j.etap.2017.03.006
Rotem R, Heyfets A, Fingrut O, Blickstein D, Shaklai M, Flescher E (2005) Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria. Cancer Res 65(5):1984–1993. https://doi.org/10.1158/0008-5472.CAN-04-3091
Salimi A, Ayatollahi A, Seydi E, Khomeisi N, Pourahmad J (2015a) Direct toxicity of amyloid beta peptide on rat brain mitochondria: preventive role of Mangifera indica and Juglans regia. Toxicol Environ Chem 97:1057–1070
Salimi A, Roudkenar MH, Sadeghi L, Mohseni A, Seydi E, Pirahmadi N, Pourahmad J (2015b) Ellagic acid, a polyphenolic compound, selectively induces ROS-mediated apoptosis in cancerous B-lymphocytes of CLL patients by directly targeting mitochondria. Redox Biol 6:461–471. https://doi.org/10.1016/j.redox.2015.08.021
Salimi A, Saharkhiz MP, Motallebi A, Seydi E, Mohseni AR, Nazemi M, Pourahmad J (2015c) Standardized extract of the Persian Gulf sponge, Axinella sinoxea selectively induces apoptosis through mitochondria in human chronic lymphocytic leukemia cells. J Anal Oncol 4:132–140
Salimi A, Motallebi A, Ayatollahi M, Seydi E, Mohseni AR, Nazemi M, Pourahmad J (2016a) Selective toxicity of Persian gulf sea cucumber holothuria parva on human chronic lymphocytic leukemia b lymphocytes by direct mitochondrial targeting. Environ Toxicol
Salimi A, Vaghar-Moussavi M, Seydi E, Pourahmad J (2016b) Toxicity of methyl tertiary-butyl ether on human blood lymphocytes. Environ Sci Pollut Res 23(9):8556–8564. https://doi.org/10.1007/s11356-016-6090-x
Salimi A, Roudkenar MH, Seydi E, Sadeghi L, Mohseni A, Pirahmadi N, Pourahmad J (2017) Chrysin as an anti-cancer agent exerts selective toxicity by directly inhibiting mitochondrial complex II and V in CLL B-lymphocytes. Cancer Investig 35(3):174–186. https://doi.org/10.1080/07357907.2016.1276187
Singh AK, Pandey P, Tewari M, Pandey HP, Shukla HS (2014) Human mitochondrial genome flaws and risk of cancer. Mitochondrial DNA 25(5):329–334. https://doi.org/10.3109/19401736.2013.796520
Talari M, Seydi E, Salimi A, Mohsenifar Z, Kamalinejad M, Pourahmad J (2014) Dracocephalum: novel anticancer plant acting on liver cancer cell mitochondria. Biomed Res Int 2014:1–10. https://doi.org/10.1155/2014/892170
Vahid A, Hadjati J, Kermanshah H, Ghabraei S (2004) Effects of cured dentin bonding materials on human monocyte viability. Oral Surg, Oral Med Oral Pathol, Oral Radiol Endodontology 98:619–621
Vevers WF, Jha AN (2008) Genotoxic and cytotoxic potential of titanium dioxide (TiO2) nanoparticles on fish cells in vitro. Ecotoxicology 17(5):410–420. https://doi.org/10.1007/s10646-008-0226-9
Wu P, Xie R, Imlay K, Shang JK (2010) Visible-light-induced bactericidal activity of titanium dioxide codoped with nitrogen and silver. Environ Sci Tech 44(18):6992–6997. https://doi.org/10.1021/es101343c
Yu K-P, Huang Y-T, Yang S-C (2013) The antifungal efficacy of nano-metals supported TiO2 and ozone on the resistant Aspergillus niger spore. J Hazard Mater 261:155–162
Zapico SC, Ubelaker DH (2014) mtDNA mutations and their role in aging, diseases and forensic sciences. Aging and Disease 4:364–380
Zhao J, Bowman L, Zhang X, Vallyathan V, Young S-H, Castranova V, Ding M (2009) Titanium dioxide (TiO2) nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid and mitochondrial pathways. J Toxic Environ Health A 72(19):1141–1149. https://doi.org/10.1080/15287390903091764
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This study was approved by the Shahid Beheshti University of Medical Sciences research ethics committee, and all healthy individuals signed an informed consent form.
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Ghanbary, F., Seydi, E., Naserzadeh, P. et al. Toxicity of nanotitanium dioxide (TiO2-NP) on human monocytes and their mitochondria. Environ Sci Pollut Res 25, 6739–6750 (2018). https://doi.org/10.1007/s11356-017-0974-2
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DOI: https://doi.org/10.1007/s11356-017-0974-2