Assessment of the toxicity of silver nanoparticles in vitro: a mitochondrial perspective.

The major toxicological concern associated with nanomaterials is the fact that some manufactured nanomaterials are redox active, and some particles transport across cell membranes, especially into mitochondria. Thus, evaluation of their toxicity upon acute exposure is essential. In this work, we evaluated the toxicity of silver nanoparticles (40 and 80 nm) and their effects in rat liver mitochondria bioenergetics. Wistar rat liver mitochondria demonstrate alterations in respiration and membrane potential capacities in the presence of either 40 or 80 nm silver nanoparticles. Our data demonstrated a statistically significant decrease in mitochondrial membrane potential, ADP-induced depolarization, and respiratory control ratio (RCR) upon exposure to silver nanoparticles. Our results show that silver nanoparticles cause impairment of mitochondrial function, due mainly to alterations of mitochondrial membrane permeability. This results in an uncoupling effect on the oxidative phosphorylation system. Thus, mitochondrial toxicity may have a central role in the toxicity resulting from exposure to silver nanoparticles.

[1]  A. Nel,et al.  Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. , 2002, Environmental health perspectives.

[2]  K. Gunter,et al.  Mitochondrial calcium transport: physiological and pathological relevance. , 1994, The American journal of physiology.

[3]  P. Oliveira,et al.  Decreased Susceptibility of Heart Mitochondria from Diabetic GK Rats to Mitochondrial Permeability Transition Induced by Calcium Phosphate , 2001, Bioscience reports.

[4]  I. Yu,et al.  Twenty-Eight-Day Oral Toxicity, Genotoxicity, and Gender-Related Tissue Distribution of Silver Nanoparticles in Sprague-Dawley Rats , 2008 .

[5]  C. Lieber,et al.  Nanowire Nanosensors for Highly Sensitive and Selective Detection of Biological and Chemical Species , 2001, Science.

[6]  Saber M Hussain,et al.  Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[7]  A. Gornall,et al.  Determination of serum proteins by means of the biuret reaction. , 1949, The Journal of biological chemistry.

[8]  J. Seagrave,et al.  The Role of a Mitochondrial Pathway in the Induction of Apoptosis by Chemicals Extracted from Diesel Exhaust Particles1 , 2000, The Journal of Immunology.

[9]  G. Rezin,et al.  In vitro effects of silver nanoparticles on the mitochondrial respiratory chain , 2010, Molecular and Cellular Biochemistry.

[10]  R M Albrecht,et al.  Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. , 2001, Journal of pharmaceutical sciences.

[11]  R. Estabrook [7] Mitochondrial respiratory control and the polarographic measurement of ADP : O ratios , 1967 .

[12]  J. Schlager,et al.  DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. , 2008, Toxicology and applied pharmacology.

[13]  J. Schlager,et al.  In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[14]  A. Nel,et al.  Chemicals in diesel exhaust particles generate reactive oxygen radicals and induce apoptosis in macrophages. , 1999, Journal of immunology.

[15]  J. James,et al.  Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[16]  P. Bernardi,et al.  Recent progress on regulation of the mitochondrial permeability transition pore; a cyclosporin-sensitive pore in the inner mitochondrial membrane , 1994, Journal of bioenergetics and biomembranes.

[17]  Erkki Ruoslahti,et al.  Nanocrystal targeting in vivo , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[18]  D. Kamp,et al.  Particulate matter induces alveolar epithelial cell DNA damage and apoptosis: role of free radicals and the mitochondria. , 2003, American journal of respiratory cell and molecular biology.

[19]  J. Gearhart,et al.  In vitro toxicity of nanoparticles in BRL 3A rat liver cells. , 2005, Toxicology in vitro : an international journal published in association with BIBRA.

[20]  M. Zoratti,et al.  The mitochondrial permeability transition. , 1995, Biochimica et biophysica acta.

[21]  Shelton D Caruthers,et al.  Nanotechnological applications in medicine. , 2007, Current opinion in biotechnology.

[22]  Robert Gelein,et al.  EXTRAPULMONARY TRANSLOCATION OF ULTRAFINE CARBON PARTICLES FOLLOWING WHOLE-BODY INHALATION EXPOSURE OF RATS , 2002, Journal of toxicology and environmental health. Part A.

[23]  Håkan Wallin,et al.  Kupffer cells are central in the removal of nanoparticles from the organism , 2007, Particle and Fibre Toxicology.

[24]  Jong Hoon Park,et al.  Comparison of acute responses of mice livers to short-term exposure to nano-sized or micro-sized silver particles , 2008, Biotechnology Letters.

[25]  Benoit Nemery,et al.  Ultrafine particles affect experimental thrombosis in an in vivo hamster model. , 2002, American journal of respiratory and critical care medicine.

[26]  Saber M Hussain,et al.  The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[27]  R. Nemanich,et al.  Multi-walled carbon nanotube interactions with human epidermal keratinocytes. , 2005, Toxicology letters.

[28]  M. Ahamed,et al.  Silver nanoparticle applications and human health. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[29]  R. L. Jones,et al.  Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. , 2008, The journal of physical chemistry. B.

[30]  M. Dempsey,et al.  Cyclosporin A is a potent inhibitor of the inner membrane permeability transition in liver mitochondria. , 1989, The Journal of biological chemistry.

[31]  C. Bonfils,et al.  Cellular localisation of a water-soluble fullerene derivative. , 2002, Biochemical and biophysical research communications.

[32]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[33]  N. Kamo,et al.  Membrane potential of mitochondria measured with an electrode sensitive to tetraphenyl phosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state , 1979, The Journal of Membrane Biology.

[34]  Taesung Kim,et al.  Lung Function Changes in Sprague-Dawley Rats After Prolonged Inhalation Exposure to Silver Nanoparticles , 2008, Inhalation toxicology.

[35]  C. Palmeira,et al.  Benzoquinone inhibits the voltage-dependent induction of the mitochondrial permeability transition caused by redox-cycling naphthoquinones. , 1997, Toxicology and applied pharmacology.