4.5 Article

One-month persistence of inflammation and alteration of fibrotic marker and cytoskeletal proteins in rat kidney after Cd-doped silica nanoparticle instillation

Journal

TOXICOLOGY LETTERS
Volume 232, Issue 2, Pages 449-457

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2014.11.021

Keywords

Cadmium; Immunohistochemistry; In vivo; Renal; Nanotoxicology; Silica

Categories

Funding

  1. Italian Ministries of Health, Research and Education
  2. Cariplo Foundation [Rif. 2011-2096]

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In vivo effects of model cadmium-containing silica nanoparticles (SiNPs-Cd, 1 mg/rat) were investigated by i.t. instillation in rats to evaluate potential effects on secondary target organ, e.g., kidney. Specific endpoints and pathological outcomes were focused to assess inflammation and fibrosis in renal tissue, 7 and 30 days after exposure to SiNPs-Cd, as well as to equivalent amount of CdCl2 or SiNPs. Immunohistochemistry was employed to investigate the presence/distribution of selected markers, i.e., (i) TGF-beta 1, (ii) IL-6 (iii) collagen (type I), (iv) fibronectin, and (v) vimentin. An ongoing inflammatory process was demonstrated, together with a general overexpression of extracellular matrix components and alteration of cytoskeletal proteins, mainly in cortex and medulla, 7 days after SiNPs-Cd, lasting until 30th day. Less pronounced effects were observed after CdCl2, while SiNPs did not cause any insult except for IL-6 expression increase. Briefly, engineered SiNPs-Cd cause long-lasting injury in rat kidney, following a single pulmonary exposure. Renal response may be due to (i) translocation, i.e., nanoparticles migration from lung to systemic circulation, or (ii) secondary organ changes, caused by circulating inflammatory factors (e.g., IL-6, TGF-beta 1) released from lung following local insult, or (iii) direct renal action of cadmium ions released from the absorbed SiNPs-Cd. (c) 2014 Elsevier Ireland Ltd. All rights reserved.

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