title: One-month persistence of inflammation and alteration of fibrotic marker and cytoskeletal proteins in rat kidney after Cd-doped silica nanoparticle instillation.
abstract: 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-ß1, (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-ß1) released from lung following local insult, or (iii) direct renal action of cadmium ions released from the absorbed SiNPs-Cd.
authors.affiliation: Laboratory of Clinical & Experimental Toxicology and Poison Control Center, Toxicology Unit, IRCCS Maugeri Foundation and University of Pavia, Via Maugeri 10, 27100 Pavia, Italy. Electronic address: teresa.coccini@fsm.it.
authors.forename: Teresa
authors.initials: T
authors.lastname: Coccini
authors.affiliation: Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, Pavia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Barni
authors.affiliation: Department of Physical Chemistry, University of Pavia, Pavia, Italy.
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Mustarelli
authors.affiliation: Laboratory of Clinical & Experimental Toxicology and Poison Control Center, Toxicology Unit, IRCCS Maugeri Foundation and University of Pavia, Via Maugeri 10, 27100 Pavia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Locatelli
authors.affiliation: Laboratory of Clinical & Experimental Toxicology and Poison Control Center, Toxicology Unit, IRCCS Maugeri Foundation and University of Pavia, Via Maugeri 10, 27100 Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Roda
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D024042:Collagen Type I; D016207:Cytokines; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D002104:Cadmium; D012822:Silicon Dioxide
keywords: Cadmium; Immunohistochemistry; In vivo; Nanotoxicology; Renal; Silica