纳米二氧化钛暴露的神经毒性作用及机制

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Abstract The toxicological effects and mechanisms of different crystal forms (anatase, rutile, mixed) and particle sizes (25, 50, 100nm) of titanium dioxide nanoparticles (TiO₂-NPs) on dopaminergic cells were thoroughly investigated using SH-SY5Y cells and PC12 cells as experimental models. The results showed that rutile TiO₂-NPs exhibited pronounced toxic effects, followed by mixed and anatase TiO₂-NPs. Furthermore, smaller particle sizes were associated with greater toxicity to nerve cells, particularly at 25nm. The neurotoxicity was related to the induction of reactive oxygen species (ROS) generation and apoptosis. The Western Blotting analysis revealed that TiO₂-NPs upregulated the levels of Bax and Cytochrome C, downregulated the expression of Bcl-2, and activated Caspase-3, indicating that TiO₂-NPs induced apoptosis of dopaminergic cells by affecting the expression of proteins related to mitochondrial apoptosis pathway.

Key words： TiO₂-NPs rutile dopaminergic cells oxidative stress apoptosis

Received: 26 February 2024

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X503

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	LIU Chao-yang
	FANG Yan-yan
	ZHANG Zhi-bing

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LIU Chao-yang,FANG Yan-yan,ZHANG Zhi-bing. The neurotoxic effects and mechanisms of titanium dioxide nanoparticles[J]. CHINA ENVIRONMENTAL SCIENCECE, 2024, 44(9): 5275-5285.

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http://www.zghjkx.com.cn/EN/ OR http://www.zghjkx.com.cn/EN/Y2024/V44/I9/5275

[1] Alex W, Paul W, Lars F, et al. Titanium dioxide nanoparticles in food and personal care products [J]. Environmental Science & Technology, 2012,46(4):2242-2250.
[2] Zhang X, Yin H, Li Z, et al. Nano-TiO₂induces autophagy to protect against cell death through antioxidative mechanism in podocytes [J]. Cell Biology and Toxicology, 2016,32(6):513-527.
[3] Shi H, Magaye R, Castranova V, et al. Titanium dioxide nanoparticles: a review of current toxicological data [J]. Particle and Fibre Toxicology, 2013,10(1):1-33.
[4] Gottschalk F, Sonderer T, Scholz R W, et al. Modeled environmental concentrations of engineered nanomaterials (TiO₂, ZnO, Ag, CNT, Fullerenes) for different regions [J]. Environmental Science & Technology, 2009,43(24):9216-9222.
[5] Liu Z, Rui M, Yu S. Occurrence of titanium dioxide nanoparticle in Taihu Lake (China) and its removal at a full-scale drinking water treatment plant [J]. Environmental Science and Pollution Research, 2021,29(16):23352-23360.
[6] Souza I, Mendes V, Duarte I, et al. Nanoparticle transport and sequestration: Intracellular titanium dioxide nanoparticles in a neotropical fish [J]. Science of the Total Environment, 2019,658:798-808.
[7] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Carbon black, titanium dioxide, and talc [M]. Lyon: International Agency for Research on Cancer, 2010:1-413.
[8] Heringa M B, Geraets L, Van E J C, et al. Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations [J]. Nanotoxicology, 2016,10(10):1515-1525.
[9] Heringa M B, Peters R J B, Bleys R, et al. Detection of titanium particles in human liver and spleen and possible health implications [J]. Particle and Fibre Toxicology, 2018,15(1):1-9.
[10] Song B, Liu J, Feng X, et al. A review on potential neurotoxicity of titanium dioxide nanoparticles [J]. Nanoscale Research Letters, 2015,10(1):1-17.
[11] Grissa I, Guezguez S, Ezzi L, et al. The effect of titanium dioxide nanoparticles on neuroinflammation response in rat brain [J]. Environmental Science and Pollution Research, 2016,23(20):20205-20213.
[12] Chen A, Liang H, Liu J, et al. Central neurotoxicity induced by the instillation of ZnO and TiO₂ nanoparticles through the taste nerve pathway [J]. Nanomedicine, 2017,12(20):2453-2470.
[13] Cui Y H, Che Y, Wang H X. Nono-titanium dioxide exposure during the adolescent period induces neurotoxicities in rats: Ameliorative potential of bergamot essential oil [J]. Brain and Behavior, 2021,11(5):e02099.
[14] Wu J, Sun J, Xue Y. Involvement of JNK and P53activation in G2/M cell cycle arrest and apoptosis induced by titanium dioxide nanoparticles in neuron cells [J]. Toxicology Letters, 2010,199(3):269-276.
[15] Jalili P, Gueniche N, Lanceleur R, et al. Investigation of the in vitro genotoxicity of two rutile TiO₂nanomaterials in human intestinal and hepatic cells and evaluation of their interference with toxicity assays [J]. NanoImpact, 2018,11:69-81.
[16] Charles S, Jomini S, Fessard V, et al. Assessment of the in vitro genotoxicity of TiO₂nanoparticles in a regulatory context [J]. Nanotoxicology, 2018,12(4):357-374.
[17] Gitrowski C, Al-jubory A R, Handy R D. Uptake of different crystal structures of TiO₂ nanoparticles by Caco-2intestinal cells [J]. Toxicol Letters, 2014,226(3):264-276.
[18] Lin X, Li J, Ma S, et al. Toxicity of TiO₂nanoparticles to Escherichia coli: effects of particle size, crystal phase and water chemistry [J]. PLoS One, 2014,9(10):e110247.
[19] Clemente Z, Castro V L, Feitosa L O, et al. Biomarker evaluation in fish after prolonged exposure to Nano-TiO₂: Influence of illumination conditions and crystal phase [J]. Journal of Nanoscience and Nanotechnology, 2015,15(7):5424-5433.
[20] Numano T, Xu J, Futakuchi M, et al. Comparative study of toxic effects of anatase and rutile type nanosized titanium dioxide particles in vivo and in vitro [J]. Asian Pacific Journal of Cancer Prevention, 2014,15(2):929-935.
[21] Sekar D, Falcioni M L, Barucca G, et al. DNA damage and repair following In vitro exposure to two different forms of titanium dioxide nanoparticles on trout erythrocyte [J]. Environmental Toxicology, 2014,29(1):117-127.
[22] Renwick L C, Donaldson K, Clouter A. Impairment of alveolar macrophage phagocytosis by ultrafine particles [J]. Toxicology and Applied Pharmacology, 2001,172(2):119-127.
[23] 方靖靖,黄昆仑,仝涛.孤独症谱系障碍实验模型研究进展[J]. 生物技术进展, 2023,13(4):509-523. Fang J J, Huang K L, Tong T. Research progress on experimental models of autism spectrum disorders [J]. Current Biotechnology, 2023,13(4):509-523.
[24] Ferraro S A, Domingo M G, Etcheverrito A, et al. Neurotoxicity mediated by oxidative stress caused by titanium dioxide nanoparticles in human neuroblastoma (SH-SY5Y) cells [J]. Journal of Trace Elements in Medicine and Biology. 2020,57:126413.
[25] Meng L, Liu C, Li Y, et al. The yeast prion protein Sup35initiates α-synuclein pathology in mouse models of Parkinson’s disease [J]. Science Advances, 2023,9(44):eadj1092.
[26] Peters R J B, van Bemmel G, Milani N B L, et al. Detection of nanoparticles in Dutch surface waters [J]. Science of the Total Environment, 2018,621:210-218.
[27] Rihane N, Nury T, M’rad I, et al. Microglial cells (BV-2) internalize titanium dioxide (TiO₂) nanoparticles: toxicity and cellular responses [J]. Environmental Science and Pollution Research, 2016,23(10):9690-9699.
[28] Gu J, Guo M, Huang C, et al. Titanium dioxide nanoparticle affects motor behavior, neurodevelopment and axonal growth in zebrafish (Danio rerio) larvae [J]. Science of the Total Environment, 2021,754:142315.
[29] Zeumer R, Galhano V, Monteiro M S, et al. Chronic effects of wastewater-borne silver and titanium dioxide nanoparticles on the rainbow trout (Oncorhynchus mykiss) [J]. Science of the Total Environment, 2020,723:137974.
[30] 刘焕亮.3种典型纳米材料生物毒性效应研究[D]. 北京:中国人民解放军军事医学科学院, 2011. Liu H L. The biotoxicity of three kinds of typical nanomaterials [D]. Beijing: Academy of Military Medical Sciences, 2011.
[31] 刘美婷,余冉,陈良辉,等.典型纳米金属氧化物对氨氧化菌Nitrosomonas europaea的生物胁迫影响[J]. 中国环境科学, 2015, 35(1):190-195. Liu M T, Yu R, Chen L H, et al. Biological effects of typical metal oxide nanoparticles on Nitrosomonas europaea [J]. China Environmental Science, 2015,35(1):190-195.
[32] Li L, Mu X, Ye L, et al. Suppression of testosterone production by nanoparticulate TiO₂is associated with ERK1/2-PKA-PKC signaling pathways in rat primary cultured Leydig cells [J]. International Journal of Nanomedicine, 2018,13:5909-5924.
[33] Zeng C, Feng Y, Wang W, et al. The size-dependent apoptotic effect of titanium dioxide nanoparticles on endothelial cells by the intracellular pathway [J]. Environmental Toxicology, 2018,33(12):1221-1228.
[34] Christensen F M, Johnston H J, Stone V, et al. Nano-TiO₂-feasibility and challenges for human health risk assessment based on open literature [J]. Nanotoxicology, 2011,5(2):110-124.
[35] Wang J, Liu Y, Jiao F, et al. Time-dependent translocation and potential impairment on central nervous system by intranasally instilled TiO₂ nanoparticles [J]. Toxicology, 2008,254(1/2):82-90.
[36] Gea M, Bonetta S, Iannarelli L, et al. Shape-engineered titanium dioxide nanoparticles (TiO₂-NPs): cytotoxicity and genotoxicity in bronchial epithelial cells [J]. Food and Chemical Toxicology, 2019, 127:89-100.
[37] 黄茜枝.海水酸化条件下纳米二氧化钛对厚壳贻贝的生态毒性效应研究[D]. 上海:上海海洋大学, 2019. Huang X Z. Ecotoxic effects of titanium dioxide nanoparticles under seawater acidification in the Thick Shell Mussel Mytilus coruscus [D]. Shanghai: Shanghai Ocean University, 2019.
[38] 吴秋霞.纳米二氧化钛在神经干细胞中的胞吞、胞排及其机理的研究[D]. 上海:上海大学, 2014. Wu Q X. Study of endocytosis and exocytosis of titanium dioxide nanoparticles and its mechanism in neural stem cells [D]. Shanghai: Shanghai University, 2014.
[39] Pérez-arizti J A, Ventura-gallegos J L, Galván juárez R E G, et al. Titanium dioxide nanoparticles promote oxidative stress, autophagy and reduce NLRP3in primary rat astrocytes [J]. Chemico-Biological Interactions, 2020,317:108966.
[40] Wu J, Xie H. Effects of titanium dioxide nanoparticles on α-synuclein aggregation and the ubiquitin-proteasome system in dopaminergic neurons [J]. Artificial Cells, Nanomedicine, and Biotechnology, 2016, 44(2):690-694.
[41] Valdiglesias V, Costa C, Sharma V, et al. Comparative study on effects of two different types of titanium dioxide nanoparticles on human neuronal cells [J]. Food and Chemical Toxicology, 2013,57:352-361.
[42] Medina-reyes E I, Rodríguez-ibarra C, Déciga-alcaraz A, et al. Food additives containing nanoparticles induce gastrotoxicity, hepatotoxicity and alterations in animal behavior: The unknown role of oxidative stress [J]. Food and Chemical Toxicology, 2020,146:111814.
[43] Wu Q, Yan W, Liu C S, et al. Parental transfer of titanium dioxide nanoparticle aggravated MCLR-induced developmental toxicity in zebrafish offspring [J]. Environmental Science Nano, 2018,5(12): 2952-2965.
[44] Liu S, Xu L, Zhang T, et al. Oxidative stress and apoptosis induced by nanosized titanium dioxide in PC12cells [J]. Toxicology, 2010, 267(1-3):172-177.
[45] Trist B G, Hare D J, Double K L. Oxidative stress in the aging substantia nigra and the etiology of Parkinson’s disease [J]. Aging Cell, 2019,18(6):e13031.
[46] Booth H D E, Hirst W D, Wade-martins R. The role of astrocyte dysfunction in Parkinson’s disease pathogenesis [J]. Trends in Neurosciences, 2017,40(6):358-370.
[47] He Q, Zhou X, Liu Y, et al. Titanium dioxide nanoparticles induce mouse hippocampal neuron apoptosis via oxidative stress-and calcium imbalance-mediated endoplasmic reticulum stress [J]. Environmental Toxicology and Pharmacology, 2018,63:6-15.
[48] Hu R, Zheng L, Zhang T, et al. Molecular mechanism of hippocampal apoptosis of mice following exposure to titanium dioxide nanoparticles [J]. Journal of Hazardous Materials, 2011,191(1-3):32-40.
[49] Zhou Y, Ji J, Chen C, et al. Retardation of axonal and dendritic outgrowth is associated with the MAPK signaling pathway in offspring mice following maternal exposure to Nanosized Titanium Dioxide [J]. Journal of Agricultural and Food Chemistry, 2019, 67(9):2709-2715.
[50] 翁文玉,郝烨华,张瑜生,等.线粒体途径相关信号通路对成骨细胞凋亡的作用[J]. 中国骨质疏松杂志, 2018,24(12):1665-1670. Weng W Y, Hao Y H, Zhang Y S, et al. The effect of mitochondrial-related signaling pathway on apoptosis of osteoblasts [J]. Chinese Journal of Osteoporosis, 2018,24(12):1665-1670.