Liver Histopathological Alteration after Repeated Intra-Tracheal Instillation of Titanium Dioxide in Male Rats
Aim: The present study designed to evaluate the toxic effect of anatase TiO2 NPs on BALF biochemical changes and liver alteration
Background: Titanium dioxide (TiO2) nanoparticles (NPs) are utilized in food color additives and cosmetics worldwide. Humans
uptake these nanoparticulate by different routes and may exhibit potential side effects, lags behind the rapid development of
Methods: Sixty-three mats rats were used. Included by the control group and the experimental groups treated twice a week with 0.5, 5,
50, 1.5, 15, 150 mg/kg of nano-TiO2 (size 21 nm), for four consecutive weeks. Animals were sacrificed at 4 days, a month and three
months post-instillation. The levels of tumor necrosis factor - ? (TNF-?) and macrophage inflammatory protein- 2 (MIP-2) were
measured in the lung homogenate and in the bronchoalveolar lavage fluid (BALF) supernatants by enzyme-linked immunosorbent assay
(ELISA) and histopathological examination of liver tissue was performed.
Results: The results showed that TiO2 NP induces many alterations in the liver structure after 4 days, a month and reduced after 3
months from intratracheal instillation. This included liver heavy infiltration of inflammatory cells, an increase of collagen density in
portal triads, beginning of fibrosis formation and Glisson capsule thickness increase and TiO2 NPs reached the liver tissue after a month
from exposure at all doses especially low doses (0.5, 1.5, 5) mg/kg of TiO2 NPs.
Conclusion: The immune system was strongly responded in the groups treated with high doses (15, 50, 150) mg/kg of TiO2 NP leading
to raising the concentration of ?-TNF, and MIP-2 in BALF while they decrease in tissue homogenate.
Keywords: Titanium dioxide effects, Liver histopathological alteration, MIP-2 changes, TiO2 effects on TNF-?.
(Please cite as: Suker DK, Jasim FA. Liver histopathological alteration after repeated intra-tracheal instillation of
titanium dioxide in male rats. Gastroenterol Hepatol Bed Bench 2018;11(2):159-168).
Fröhlich, E. (2012). The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles. International Journal of Nanomedicine, 7, 5577–5591.
Kettler, K., Veltman, K., van de Meent, D., van Wezel, A., & Hendriks, A. J. (2014). Cellular uptake of nanoparticles as determined by particle properties, experimental conditions, and cell type. Environmental Toxicology and Chemistry, 33(3), 481–492.
Barua, S. & Mitragotri, S. (2014). Challenges associated with Penetration of Nanoparticles across Cell and Tissue Barriers: A review of current status and future prospects. Nano Today, 9(2), 223–243.
Chang, X., Zhang, Y., Tang, M., & Wang, B. (2013). Health effects of exposure to nano-TiO2: a meta-analysis of experimental studies. Nanoscale Research Letters, 8(1), 51.
Faddah, L. M., Abdel Baky, N. A., Al-Rasheed, N. M., & Al-Rasheed, N. M. (2013). Biochemical responses of nanosize titanium dioxide in the heart of rats following administration of idepenone and quercetin. African Journal of Pharmacy and Pharmacology, 7(38), 2639–2651.
Bhattacharjee, S., Ershov, D., Fytianos, K., van der Gucht, J., Alink, G. M., Rietjens, I. M., Marcelis A. T. M. & Zuilhof, H. (2012). Cytotoxicity and cellular uptake of tri-block copolymer nanoparticles with different size and surface characteristics. Particle and Fiber Toxicology, 9(1), 11.
Duffield, J. S., Lupher, M., Thannickal, V. J., & Wynn, T. A. (2013). Host responses in tissue repair and fibrosis. Annual Review of Patholology, 8(October), 241–276.
Corneanu, G., & Craciun, C. (2010). The eukaryote cell interaction with doped TiO2 nanoparticles. Romanian Inventory and Networking for Integration in ERA, 20.
Jasim, F. A., Suker, D. K., & Albadran, A. I. (2017). TiO 2 Nanoparticles Induce Lung Fibrosis and Proteinosis through Influence on Matrix Metalloproteinase Expression, 1–13.
Boyer, L., Plantier, L., Dagouassat, M., Lanone, S., Goven, D., Caramelle, P., Berrehar F., kerbrat S., Dinh-Xuan A.-T., Crestani B., Gouvello S. L. & Boczkowski, J. (2011). Role of nitric oxide synthases in elastase-induced emphysema. Laboratory Investigation; a Journal of Technical Methods and Pathology, 91(3), 353–62.
Shani, W.S. (2012) Practical immunology textbook. 1st ed., 2456 Bagdad, Iraq.
Drury, R. A. B., Wallington, E. A. & Carmeron, Sir R. (1967) Carleton’s histological technique. 4th ed. Oxford University Press, London, England., 129-133.
MacSween, R. N. M. & Whaley, K. (1992). Muir’s textbook of pathology. 13th ed. Educational low-Priced Books Scheme, British Government.
Moon, C., Park, H.-J., Choi, Y.-H., Park, E.-M., Castranova, V., & Kang, J. L. (2010). Pulmonary inflammation after intraperitoneal administration of ultrafine titanium dioxide (TiO2) at rest or in lungs primed with lipopolysaccharide. Journal of Toxicology and Environmental Health. Part A, 73(5), 396–409.
Matute-Bello, G., Winn, R. K., Jonas, M., Chi, E. Y., Martin, T. R., & Liles, W. C. (2001). Fas (CD95) induces alveolar epithelial cell apoptosis in vivo: implications for acute pulmonary inflammation. American Journal Pathology, 158(1), 153–161.
Cho, W.-S., Duffin, R., Bradley, M., Megson, I. L., MacNee, W., Lee, J. K., Jeong J. K. & Donaldson, K. (2013). Predictive value of in vitro assays depends on the mechanism of toxicity of metal oxide nanoparticles. Particle and Fiber Toxicology, 10(1), 55.
Iavicoli, I., Leso, V., Fontana, L., & Bergamaschi, A. (2012). Toxicological effects of titanium dioxide nanoparticles: A review of in vitro mammalian studies. Hindawi Publishing Corporation Journal of Nanomaterials, 2012, 36.
Wang, J., Zhou, G., Chen, C., Yu, H., Wang, T., Ma, Y., Jai G., Gao Y., Li B., Sun J., Li Y., Jiao F., Zhao Y. & Chai, Z. (2007). Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicology Letters, 168(2), 176–185.
Ma, L., Zhao, J., Wang, J., Liu, J., Duan, Y., Liu, H., Li N., Yan J., Ruan J., Wang H. & Hong, F. (2009). The Acute Liver Injury in Mice Caused by Nano-Anatase TiO2. Nanoscale Research Letters, 4, 1275–1285.
Miranda, R. R., Damaso da Silveira, A. L. R., de Jesus, I. P., Grötzner, S. R., Voigt, C. L., Campos, S. X., Garcia J. R. E., Randi M. A.F., Oliveira Ribeiro C. A. & Filipak Neto, F. (2016). Effects of realistic concentrations of TiO2 and ZnO nanoparticles in prochilodus lineatus juvenile fish. Environmental Science and Pollution Research, 23(6), 5179–5188.
Federici, G., Shaw, B. J., & Handy, R. D. (2007). Toxicity of titanium dioxide nanoparticles to rainbow trout (Oncorhynchus mykiss): Gill injury, oxidative stress, and other physiological effects. Aquatic Toxicology, 84(4), 415–430.
Madala, S. K., Pesce, J. T., Ramalingam, T. R., Wilson, M. S., Minnicozzi, S., Cheever, A. W., Thompson R. W., Mertink-Kane M. M. & Wynn, T. A. (2010). Matrix metalloproteinase 12 deficiency augments extracellular matrix degrading metalloproteinases and attenuates IL-13 dependent fibrosis. The Journal of Immunology, 184(7), 3955–3963.
Roderfeld, M., Hemmann, S., & Roeb, E. (2007). Mechanisms of fibrolysis in chronic liver injury (with special emphasis on MMPs and TIMPs). Zeitschrift Fur Gastroenterologie, 45(1), 25–33.
Natarajan, V., Wilson, C. L., Hayward, S. L., & Kidambi, S. (2015). Titanium dioxide nanoparticles trigger loss of function and perturbation of mitochondrial dynamics in primary hepatocytes. PLoS ONE, 10(8), 1–19.
Duan, Y., Liu, J., Ma, L., Li, N., Liu, H., Wang, J., Zheng L., Liu C., Wang X., Zhao X., Yan J., Wang S., Wang H., Zhang X. & Hong, F. (2010). Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice. Biomaterials, 31(5), 894–899.
Fatemeh, M. F., & Mohammad, F. (2014). The histological and biochemical effects of titanium dioxide nanoparticle (TiO2) on the liver in wistar Rat. International Research Journal of Biological Sciences, 3(6), (2278–3202), 1–5.
Yoshioka, K., Mori, a, Taniguchi, K., & Mutoh, K. (2005). Cell proliferation activity of proliferating bile duct after bile duct ligation in rats. Veterinary Pathology, 42(3), 382–5.
Burt, A. D., & MacSween, R. N. M. (1993). Bile duct proliferation? Its true significance? Histopathology, 23(6), 599–602.