title: Pulmonary toxicity of instilled cadmium-doped silica nanoparticles during acute and subacute stages in rats.
abstract: Potential risk associated with new nanomaterial exposure needs to be assessed. This in vivo study investigated pulmonary effects of engineered cadmium-containing silica nanoparticles Cd/SiNPs (1 mg/rat), silica SiNPs (600 μg/rat) and CdCl₂ (400 μg/rat) 1, 7 and 30 days after intratracheal instillation. Comprehensive histopathological and immunocytochemical characterization of lung damage in terms of apoptosis, cell proliferation, inflammation, fibrosis and metabolism were obtained.  After exposure to all treatments, lung parenchyma showed injury patterns characterized by collapsed alveoli, inflammation, granuloma formation, thickened alveolar septa and bronchiolar epithelium exfoliation. Type II pneumocytes, containing scarcely surfactant-lamellated bodies, were also observed. Apoptotic phenomena enhanced as following, Cd/SiNPs>CdCl₂> SiNPs. In parallel with these findings, a significant increase of PCNA-immunoreactive cells was detected together with high mitotic activity. Cellular localization and distribution of IL-6, IP-10 and TGF-β1 revealed an increased expression of these cytokines as evidence of an enhanced cellular inflammatory response. CYP450-immunoreactivity was also enhanced, at bronchiolar (e.g. Clara cells) and alveolar (e.g. macrophages) level after both Cd/SiNPs and CdCl₂. These overall effects were observed acutely and lasted until the 30th day, with Cd/SiNPs producing the most marked effects.   Collagen-immunolabelling changed particularly 7 and 30 days after Cd/SiNPs, when a strong stromal fibrogenic reaction occurred.   The present findings suggest that Cd/SiNPs produce significantly greater pulmonary alterations than either SiNPs or CdCl₂ under the present experimental conditions.
authors.affiliation: Salvatore Maugeri Foundation IRCCS, Toxicology Division, University of Pavia, Pavia, Italy. teresa.coccini@fsm.it
authors.forename: Teresa
authors.initials: T
authors.lastname: Coccini
authors.forename: Sergio
authors.initials: S
authors.lastname: Barni
authors.forename: Rita
authors.initials: R
authors.lastname: Vaccarone
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Mustarelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Manzo
authors.forename: Elisa
authors.initials: E
authors.lastname: Roda
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019256:Cadmium Chloride / Q000009:adverse effects* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000378:metabolism; D005355:Fibrosis; D015850:Interleukin-6 / Q000378:metabolism; D055370:Lung Injury / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D023421:Models, Animal; D053758:Nanoparticles / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D012822:Silicon Dioxide / Q000009:adverse effects* / Q000494:pharmacology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D054357:Chemokine CXCL10; C091326:Cxcl10 protein, rat; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D012822:Silicon Dioxide; D019256:Cadmium Chloride