Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats

Titanium dioxide (TiO2) nanoparticles are among the top five nanoparticles used in consumer products, paints, and pharmaceutical preparations. Given that exposure to such nanoparticles is mainly via the skin and inhalation, the present study was conducted in male Wistar albino rats (Rattus norvegicus). Our aim was to investigate the effect of TiO2 nanoparticles on hepatic tissue in an attempt to understand their toxicity and the potential effect of their therapeutic and diagnostic use. To investigate the effects of TiO2 nanoparticles on liver tissue, 30 healthy male Wistar albino rats were exposed to TiO2 nanoparticles at doses of 63 mg, 126 mg, and 252 mg per animal for 24 and 48 hours. Serum glutamate oxaloacetate transaminase and alkaline phosphatase activity was altered. Changes in hepatocytes can be summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltration by chronic inflammatory cells, and congested dilated central veins. The histologic alterations observed might be an indication of hepatocyte injury due to the toxicity of TiO2 nanoparticles, resulting in an inability to deal with accumulated residues from the metabolic and structural disturbances caused by these nanoparticles. The appearance of cytoplasmic degeneration and destruction of nuclei in hepatocytes suggests that TiO2 nanoparticles interact with proteins and enzymes in hepatic tissue, interfering with antioxidant defense mechanisms and leading to generation of reactive oxygen species which, in turn, may induce stress in hepatocytes, promoting atrophy, apoptosis, and necrosis. More immunohistochemical and ultrastructural investigations are needed in relation to TiO2 nanoparticles and their potential effects when used as therapeutic and diagnostic tools.

[1]  J. Everitt,et al.  Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.

[2]  J. Petković,et al.  Titanium dioxide in our everyday life; is it safe? , 2011, Radiology and oncology.

[3]  J. Yi,et al.  Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation. , 2009, Toxicology.

[4]  Min-Kyeong Yeo,et al.  The biological toxicities of two crystalline phases and differential sizes of TiO2 nanoparticles during zebrafish embryogenesis development , 2012, Molecular & Cellular Toxicology.

[5]  Saber M Hussain,et al.  Metal-based nanoparticles and their toxicity assessment. , 2010, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[6]  G. Oberdörster,et al.  Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles , 2005, Environmental health perspectives.

[7]  Kevin E. Driscoll,et al.  Cytokine and Growth Factor Release by Alveolar Macrophages: Potential Biomarkers of Pulmonary Toxicity 1 , 1991, Toxicologic pathology.

[8]  Jongheop Yi,et al.  Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells. , 2008, Toxicology letters.

[9]  R. Baggs,et al.  Regression of Pulmonary Lesions Produced by Inhaled Titanium Dioxide in Rats , 1997, Veterinary pathology.

[10]  A. Gedanken,et al.  Selective cytotoxic effect of ZnO nanoparticles on glioma cells , 2009 .

[11]  Yu-feng Li,et al.  Fate and toxicity of metallic and metal-containing nanoparticles for biomedical applications. , 2011, Small.

[12]  N. Tietz Fundamentals of Clinical Chemistry , 1970 .

[13]  Karluss Thomas,et al.  Research strategies for safety evaluation of nanomaterials, part VII: evaluating consumer exposure to nanoscale materials. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[14]  Gwendolyn R. Goss,et al.  Theory and Practice of Histological Techniques , 2009 .

[15]  Kazutaka Hirakawa,et al.  Photo-irradiated Titanium Dioxide Catalyzes Site Specific DNA Damage via Generation of Hydrogen Peroxide , 2004, Free radical research.

[16]  Pei-Xun Liu,et al.  Toxicologic effects of gold nanoparticles in vivo by different administration routes , 2010, International journal of nanomedicine.

[17]  B. Giray,et al.  Cypermethrin-induced oxidative stress in rat brain and liver is prevented by vitamin E or allopurinol. , 2001, Toxicology letters.

[18]  S. Doak,et al.  NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. , 2009, Biomaterials.

[19]  J. Haines,et al.  International programme on chemical safety , 1996, The Lancet.

[20]  M. Los,et al.  Inflammatory response, reactive oxygen species, programmed (necrotic-like and apoptotic) cell death and cancer. , 2004, Roczniki Akademii Medycznej w Bialymstoku.

[21]  Amanda S Barnard,et al.  One-to-one comparison of sunscreen efficacy, aesthetics and potential nanotoxicity. , 2010, Nature nanotechnology.

[22]  Jose R Peralta-Videa,et al.  Nanomaterials and the environment: a review for the biennium 2008-2010. , 2011, Journal of hazardous materials.

[23]  Amy K Madl,et al.  Health effects of inhaled engineered and incidental nanoparticles , 2009, Critical reviews in toxicology.

[24]  Zhi Pan,et al.  Adverse effects of titanium dioxide nanoparticles on human dermal fibroblasts and how to protect cells. , 2009, Small.

[25]  Edward R. Ashwood,et al.  Tietz Fundamentals of Clinical Chemistry , 1996 .

[26]  Vicki Stone,et al.  Identification of the mechanisms that drive the toxicity of TiO2 particulates: the contribution of physicochemical characteristics , 2009, Particle and Fibre Toxicology.

[27]  T. Xia,et al.  Toxic Potential of Materials at the Nanolevel , 2006, Science.

[28]  T. Stokke,et al.  Binucleation and polyploidization patterns in developmental and regenerative rat liver growth , 1993, Cell proliferation.

[29]  T. Webb,et al.  Pulmonary toxicity study in rats with three forms of ultrafine-TiO2 particles: differential responses related to surface properties. , 2007, Toxicology.

[30]  B. Bay,et al.  Nanoparticle-induced pulmonary toxicity , 2010, Experimental biology and medicine.