Isoprostanes as Biomarkers for In Vivo Evaluation of Nanoparticle-induced Oxidative Stress: a Study with Silica Nanoparticles Doped with Cadmium

The application of silica/cadmium containing nanomaterials in medicine and technology has attracted much attention in the latest years. However, 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 mg/rat), or SiNPs (600 mg/rat) have been investigated by evaluating F2-isoprostanes (F2-IsoPs) and superoxide dismutase (SOD1) as markers of oxidative stress 24 hr, 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 expression in pulmonary tissue by immunocytochemistry. The present paper also gives an overview of current scientific knowledge and application of F2-IsoPs as oxidative stress markers. 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 post-exposure. Pulmonary SOD1-immunoreactivity was significantly enhanced in a time-dependent manner (7 days <30 days) after both CdCl2 and SiNPs-Cd treatments with the latter causing more pronounced effects. SiNPs did not influence SOD1-immunolabeling. The results indicate the (i) potential of engineered SiNPs-Cd to cause long-lasting oxidative tissue injury following pulmonary exposure in rat and (ii) a possible role for plasma F2-IsoPs measurement as a predictive indicator of nanoparticle-induced oxidative insult.