Abstract
While nephrotoxicity of cadmium is well documented, very limited information exists on renal effects of exposure to cadmium-containing nanomaterials. In this work, “omics” methodologies have been used to assess the action of cadmium-containing silica nanoparticles (Cd-SiNPs) in the kidney of Sprague-Dawley rats exposed intratracheally. Groups of animals received a single dose of Cd-SiNPs (1 mg/rat), CdCl2 (400 μg/rat) or 0.1 ml saline (control). Renal gene expression was evaluated 7 and 30 days post exposure by DNA microarray technology using the Agilent Whole Rat Genome Microarray 4x44K. Gene modulating effects were observed in kidney at both time periods after treatment with Cd-SiNPs. The number of differentially expressed genes being 139 and 153 at the post exposure days 7 and 30, respectively. Renal gene expression changes were also observed in the kidney of CdCl2-treated rats with a total of 253 and 70 probes modulated at 7 and 30 days, respectively. Analysis of renal gene expression profiles at day 7 indicated in both Cd-SiNP and CdCl2 groups downregulation of several cluster genes linked to immune function, oxidative stress, and inflammation processes. Differing from day 7, the majority of cluster gene categories modified by nanoparticles in kidney 30 days after dosing were genes implicated in cell regulation and apoptosis. Modest renal gene expression changes were observed at day 30 in rats treated with CdCl2. These results indicate that kidney may be a susceptible target for subtle long-lasting molecular alterations produced by cadmium nanoparticles locally instilled in the lung.
Similar content being viewed by others
References
ATSDR (Agency for toxic substances and disease registry) (2008) Toxicological profile for cadmium (Draft for Public Comment). U.S. Department of Health and Human Services, Public Health Service, Atlanta, GA
Chargui A, Zekri S, Jaquillet G, Rubera I, Ilie M, Belaid A, Duranton C, Tauc M, Hofman P, Poujeol P, El May MV, Mograbi B (2011) Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure. Toxicol Sci 121:31–42
Cho M, Cho W-S, Choi M, Kim SJ, Han BS, Kim SH, Kim HO, Sheen YY, Jeong J (2009) The impact of size on tissue distribution and elimination by single intravenous injection of silica nanoparticles. Toxicol Lett 189:177–183
Choi HS, Ashitate Y, Lee JH, Kim SH, Matsui A, Insin N, Bawendi MG, Semmler-Behnke M, Frangioni JV, Tsuda A (2010) Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol 28:1300–1303
Coccini T, Fabbri M, Roda E, Sacco MG, Manzo L, Gribaldo L (2011) Gene expression analysis in rat lung after intratracheal exposure to nanoparticles doped with cadmium. J Physics Conf Ser 304. doi:10.1088/1742-6596/304/1/012025
Damiano VV, Cherian PV, Frankel FR, Steeger JR, Sohn M, Oppenheim D, Weinbaum G (1990) Intraluminal fibrosis induced unilaterally by lobar instillation of CdCl2 into the rat lung. Am J Pathol 137:883–894
Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA (2003) DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 4:P3
Descotes J (1992) Immunotoxicology of cadmium. IARC Sci Publ 118:385–390
Driscoll KE, Maurer JK, Poynter J, Higgins J, Asquith T, Miller NS (1992) Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis. Toxicol Appl Pharmacol 116:30–37
Driscoll KE, Costa DL, Hatch G, Henderson R, Oberdörster G, Salem H, Schlesinger RB (2000) Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations. Toxicol Sci 55:24–25
Ekins S, Bugrim A, Brovold L, Kirillov E, Nikolsky Y, Rakhmatulin E, Sorokina S, Ryabov A, Serebryiskaya T, Melnikov A et al (2006) Algorithms for network analysis in systems-ADME/Tox using the MetaCore and MetaDrug platforms. Xenobiotica 36:877–901
Goodsaid FM (2004) Identification and measurement of genomic biomarkers of nephrotoxicity. J Pharmacol Toxicol Methods 49:183–186
Gopee NV, Roberts DW, Webb P, Cozart CR, Siitonen PH, Warbritton AR, Yu WW, Colvin L, Walker NJ, Howard PC (2007) Migration of intradermally injected quantum dots to sentinel organs in mice. Toxicol Sci 98:249–257
Goyer RA, Cherian MG, Delaquerriere-Richardson L (1984) Correlation of parameters of cadmium exposure with onset of cadmium-induced nephropathy in rats. J Environ Pathol Toxicol Oncol 5:89–100
Hou J, Goodenough DA (2010) Claudin-16 and claudin-19 function in the thick ascending limb. Curr Opin Nephrol Hypertens 19:483–488
Kondo C, Minowa Y, Uehara T, Okuno Y, Nakatsu N, Ono A, Maruyama T, Kato I, Yamate J, Yamada H, Ohno Y, Urushidani T (2009) Identification of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database. Toxicology 265:15–26
Kreyling WG, Semmler-Behnke M, Seitz J, Scymczak W, Wenk A, Mayer P, Takenaka S, Oberdörster G (2009) Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs. Inhal Toxicol 21S1:55–60
Limbach LK, Wick P, Manser P, Grass RN, Bruinink A, Stark WJ (2007) Exposure of engineered nanoparticles to human lung epithelial cells: influence of chemical composition and catalytic activity on oxidative stress. Environ Sci Technol 41:4158–4163
Liu J, Cu W, Kadiiska MB (2009) Role of oxidative stress in cadmium-toxicity and carcinogenesis. Toxicol Appl Pharmacol 238:209–214
Mitchell LA, Lauer FT, Burchiel SW, McDonand JD (2009) Mechanisms for how inhaled multiwalled carbon nanotubes suppress systemic immune function in mice. Nat Nanotechnol 4:451–456
Napierska D, Thomassen LCJ, Lison D, Martens JA, Hoet PE (2010) The nanosilica hazard: another variable entity. Part Fibre Toxicol 7:39. doi:10.1186/1743-8977-7-39. http://www.particleandfibretoxicology.com/content/7/1/39
Nogawa K, Honda R, Yamada Y, Kido T, Tsuritani I, Ishizaki M, Yamaya H (1986) Critical concentration of cadmium in kidney cortex in humans exposed to environmental cadmium. Environ Res 40:251–260
Nogué S, Sanz-Gallén P, Torras A, Boluda F (2004) Chronic overexposure to cadmium fumes associated with IgA mesangial glomerulonephritis. Occup Med 54:265–267
Nordberg GF, Onawa K, Nordberg M, Friberg LT (2007) Cadmium. In: Nordberg GF, Fowler BA, Nordberg M, Friberg LT (eds) Handbook of toxicology of metals, 3rd edn. Elsevier, Amsterdam
Oberdörster G (1992) Pulmonary deposition, clearance and effects of inhaled soluble and insoluble cadmium compounds. In: Nordberg GF, Herber RFM, Alessio L (eds) Cadmium in the human environment: toxicity and carcinogenicity. International Agency for Research on Cancer, Lyon, pp 189–204
Oberdörster G, Baumert H-P, Hochrainer D (1979) The clearance of cadmium aerosols after inhalation exposure. Am Ind Hyg Assoc J 40:443–450
Oberdörster G, Cherian MG, Baggs RB (1994) Importance of species differences in experimental pulmonary carcinogenicity of inhaled cadmium for extrapolation to humans. Toxicol Lett 72:339–343
Ozaki K, Matheis KA, Gamber M, Feidl T, Nolte T, Kalkuhl A, Deschl U (2010) Identification of genes involved in gentamicin-induced nephrotoxicity in rats: a toxicogenomic investigation. Exp Toxicol Pathol 62:555–566
Park E-J, Yi J, Kim Y, Choi K, Park K (2010) Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism. Toxicol in Vitro 24:872–878
Prozialeck WC, Edwards JR (2007) Cell adhesion molecules in chemically-induced renal injury. Pharmacol Ther 114:74–93
Prozialeck WC, Edwards JR, Wood JM (2006) The vascular endothelium as a target of cadmium toxicity. Life Sci 79:1493–1506
Rzigalinski BA, Strobl JS (2010) Cadmium-containing nanoparticles: perspectives on pharmacology and toxicology of quantum dots. Toxicol Appl Pharmacol 238:380–388
Saeed AI, Bhagabati NK, Braisted JC, Liang W, Sharow V, Howe EA, Li J, Thiagarajan M, White JA, Quackenbush J (2006) TM4 microarray software suite. Methods Enzymol 411:134–193
Savolainen K, Pylkkanen L, Norppa H, Falck G, Lindberg H, Tuomi T, Vippola M, Alenius H, Hameri K, Koivisto J, Brouwer D, Mark D, Bard D, Berges M, Jankowska E, Posniak M, Farmer P, Singh R, Krombach F, Bhari P, Kasper G, Seipenbusch M (2010) Nanotechnologies, engineered nanomaterials and occupational health and safety: a review. Saf Sci 48:857–963
Schmid H, Henger A, Kretzler M (2006) Molecular approaches to chronic kidney disease. Curr Opin Nephrol Hypertens 15:123–129
Shiohara A, Hoshino A, Hanaki K, Suzuki K, Yamamoto K (2004) On the cytotoxicity caused by quantum dots. Microbiol Immunol 48:669–675
Shvedova AA, Kisin ER, Mercer R, Murray A, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P (2005) Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289:L698–L708
Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3: article 3
Thévenod F (2009) Cadmium and cellular signalling cascades: to be or not to be? Toxicol Appl Pharmacol 238:221–239
Vivero-Escoto JL, Slowing II, Trewyn BG, Lin VS (2010) Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small 6:1952–1967
Wang S-H, Shih Y-L, Lee C–C, Chen W-L, Lin C-J, Lin Y-S, Wu K-H, Shih C-M (2009) The role of endoplasmic reticulum in cadmium-induced mesangial cell apoptosis. Chem Biol Interact 181:45–51
Wilmes A, Crean D, Aydin S, Pfaller W, Jennings P, Leonard MO (2011) Identification and dissection of the Nrf2 mediated oxidative stress pathway in human renal proximal tubule toxicity. Toxicol in Vitro 25:613–622
Xiao W, Liu Y, Templeton DM (2009) Pleiotropic effects of cadmium in mesangial cells. Toxicol Appl Pharmacol 238:315–326
Yamaguchi M (2005) Role of regucalcin in maintaining cell homeostasis and function. Int J Mol Med 15:371–389 (review)
Yeung KY, Haynor DR, Ruzzo WL (2001) Validating clustering for gene expression data. Bioinformatics 17:309–318
Acknowledgments
Nanoparticles (Cd-SiNPs) were prepared, characterized, and kindly provided by Prof. Piercarlo Mustarelli, University of Pavia Department of Physical Chemistry. We would like to thank CAMCOR team, University of Oregon (Eugene, OR, USA) for the valuable support and assistance on the physicochemical characterization of Cd/SiNPs. Work supported by Grants from the European Commission, Italian Ministry of Health, Italian Ministry of Research and Education, CARIPLO Foundation (Rif. 2009–2440). The authors wish to acknowledge Mr. Davide Acerbi for his excellent technical assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
Special Issue Editors: Candace S.-J. Tsai, Michael J. Ellenbecker
This article is part of the Topical Collection on Nanotechnology, Occupational and Environmental Health
Rights and permissions
About this article
Cite this article
Coccini, T., Roda, E., Fabbri, M. et al. Gene expression profiling in rat kidney after intratracheal exposure to cadmium-doped nanoparticles. J Nanopart Res 14, 925 (2012). https://doi.org/10.1007/s11051-012-0925-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11051-012-0925-2