Long-lasting oxidative pulmonary insult in rat after intratracheal instillation of silica nanoparticles doped with cadmium.
Silica/cadmium containing nanomaterials are now produced on industrial scale due to their potential for a variety of technological applications. Nevertheless, information on toxicity, exposure and health impact of these nanomaterials is still limited. In this study, in vivo effects of silica nanoparticles (SiNPs) doped with Cd (SiNPs-Cd, 1mg/rat), soluble CdCl(2) (400 μg/rat), or SiNPs (600 μg/rat) have been investigated by evaluating F(2)-isoprostanes (F(2)-IsoPs), superoxide dismutase (SOD1), inducible nitric oxide synthase (iNOS) and cyclooxygenase type 2 (COX-2) enzymes, as markers of oxidative stress, 24h, 7 and 30 days after intra-tracheal (i.t.) instillation to rats. Free and esterified F(2)-IsoPs were evaluated in lung and plasma samples by GC/NICI-MS/MS analysis, and SOD1, iNOS and COX-2 expression in pulmonary tissue by immunocytochemistry. Thirty days after exposure, pulmonary total F(2)-IsoPs were increased by 56% and 43% in CdCl(2) and SiNPs-Cd groups, respectively, compared to controls (32.8 ± 7.8 ng/g). Parallel elevation of free F(2)-IsoPs was observed in plasma samples (by 113% and 95% in CdCl(2) and SiNPs-Cd groups, respectively), compared to controls (28 ± 8 pg/ml). These effects were already detectable at day 7 and lasted until day 30 post-exposure. Pulmonary SOD1-, iNOS-, and COX-2-immunoreactivity was significantly enhanced in a time-dependent manner (7 days <30 days) after both CdCl(2) and SiNPs-Cd treatments. SiNPs did not influence any of the evaluated endpoints. The results indicate the capacity of engineered SiNPs-Cd to cause long-lasting oxidative tissue injury following pulmonary exposure in rat.
Salvatore Maugeri Foundation IRCCS Institute of Pavia, and University of Pavia, Toxicology Division and European Centre for Nanomedicine, Pavia, Italy. teresa.coccini@fsm.it
Teresa
T
Coccini
Elisa
E
Roda
Sergio
S
Barni
Cinzia
C
Signorini
Luigi
L
Manzo
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002104:Cadmium / Q000633:toxicity*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D028441:F2-Isoprostanes / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017348:Microscopy, Electron, Scanning Transmission; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014961:X-Ray Diffraction
D028441:F2-Isoprostanes; D002104:Cadmium; D012822:Silicon Dioxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1