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, 1 mg/rat), soluble CdCl2 (400 μg/rat), or SiNPs (600 μg/rat) have been investigated by evaluating F2-isoprostanes (F2-IsoPs), superoxide dismutase (SOD1), inducible nitric oxide synthase (iNOS) and cyclooxygenase type 2 (COX-2) enzymes, as markers of oxidative stress, 24 h, 7 and 30 days after intra-tracheal (i.t.) instillation to rats. Free and esterified F2-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 F2-IsoPs were increased by 56% and 43% in CdCl2 and SiNPs-Cd groups, respectively, compared to controls (32.8 ± 7.8 ng/g). Parallel elevation of free F2-IsoPs was observed in plasma samples (by 113% and 95% in CdCl2 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 postexposure. Pulmonary SOD1-, iNOS-, and COX-2-immunoreactivity was significantly enhanced in a timedependent manner (7 days <30 days) after both CdCl2 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