Nanoparticulate-induced toxicity and related mechanism in vitro and in vivo

In urban areas, the quantity of exhaust particles from vehicle emissions is tremendous and has been regarded as the main contributor to particulate matter (PM) pollution. Recently, the nano-sized PM on public health has begun to raise the attention. The increased toxicity of nanoparticulate can be largely explained by their small size, high airborne concentration, extensive surface area and high content of organic carbon and transition metals. We have attempted to address the toxicity of nano sized-particlulate matter by comparing various particulates including micro-SiO2 (mSiO2), nano-SiO2 (nSiO2), micro-TiO2 (mTiO2), and nano-TiO2 (nTiO2) in RAW264.7 cells and in vivo. The cell viability of all particulates decreased dose dependently. 24-h incubation with nSiO2 demonstrated apoptosis in RAW264.7 using Annexin-V binding immunofluorescent microscopy, but not in any other particulates. In vivo, cytotoxicity of nanosized was higher than micro-sized particulates. As higher the concentration of particulates, the more pulmonary injury and neutrophilic infiltration were observed in nano-sized than micro-sized particulates, respectively. Particularly, 5.0 mg/kg of mTiO2 never shows any increase of neutrophile even with high cellularity of total cells and macrophages. From these results, we suggested that particulate-induced respiratory toxicity be influenced by component, size, and dose of particulates including the characteristic nature of the target cells in vitro and in vivo.

[1]  H. Uchino,et al.  DEPARTMENT OF INTERNAL MEDICINE , 1966 .

[2]  F. Afaq,et al.  Cytotoxicity, pro‐oxidant effects and antioxidant depletion in rat lung alveolar macrophages exposed to ultrafine titanium dioxide , 1998, Journal of applied toxicology : JAT.

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

[4]  Ning Li,et al.  Comparison of the Pro-Oxidative and Proinflammatory Effects of Organic Diesel Exhaust Particle Chemicals in Bronchial Epithelial Cells and Macrophages1 , 2002, The Journal of Immunology.

[5]  K. Chung,et al.  Regulation of human lung epithelial cell numbers by diesel exhaust particles , 2006, European Respiratory Journal.

[6]  Günter Oberdörster,et al.  Ultrafine particles in the urban air: to the respiratory tract--and beyond? , 2002, Environmental health perspectives.

[7]  Qamar Rahman,et al.  Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts. , 2002, Environmental health perspectives.

[8]  T. Gilmore,et al.  Control of apoptosis by Rel/NF-κB transcription factors , 1999, Oncogene.

[9]  F. Dominici,et al.  Fine particulate air pollution and mortality in 20 U.S. cities, 1987-1994. , 2000, The New England journal of medicine.

[10]  I. Yamadori,et al.  TITANIUM DIOXIDE DEPOSITION AND ADENOCARCINOMA OF THE LUNG , 1986, Acta pathologica japonica.

[11]  M. Morandi,et al.  A Comparison of Murine and Human Alveolar Macrophage Responses to Urban Particulate Matter , 2004, Inhalation toxicology.

[12]  Robert Gelein,et al.  Role of the alveolar macrophage in lung injury: studies with ultrafine particles. , 1992 .

[13]  D. Bowden Macrophages, dust, and pulmonary diseases. , 1987, Experimental lung research.

[14]  F. Marcheselli,et al.  Crystalline silica induces apoptosis in human endothelial cells in vitro , 2004, Cell Biology and Toxicology.

[15]  Lang Tran,et al.  Safe handling of nanotechnology , 2006, Nature.

[16]  W. Rom,et al.  Basic pathogenetic mechanisms in silicosis: current understanding , 2005, Current opinion in pulmonary medicine.

[17]  Thomas H Thatcher,et al.  OROPHARYNGEAL ASPIRATION OF A SILICA SUSPENSION PRODUCES A SUPERIOR MODEL OF SILICOSIS IN THE MOUSE WHEN COMPARED TO INTRATRACHEAL INSTILLATION , 2006, Experimental lung research.

[18]  Stephen S. Olin,et al.  THE RELEVANCE OF THE RAT LUNG RESPONSE TO PARTICLE OVERLOAD FOR HUMAN RISK ASSESSMENT: A Workshop Consensus Report , 2000, Inhalation toxicology.

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

[20]  P. Schwarze,et al.  Chemical composition and not only total surface area is important for the effects of ultrafine particles. , 2006, Mutation research.

[21]  D. Bates The Particulate Whodunit: Introductory Remarks for Integrative Summary Session , 2000 .

[22]  David B Warheit,et al.  Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[23]  K. Driscoll,et al.  The comparison of a fibrogenic and two nonfibrogenic dusts by bronchoalveolar lavage. , 1990, Toxicology and applied pharmacology.

[24]  B. Brunekreef,et al.  IMMUNE BIOMARKERS IN RELATION TO EXPOSURE TO PARTICULATE MATTER: A Cross-Sectional Survey in 17 Cities of Central Europe , 2000, Inhalation toxicology.