Jornal de Biomarcadores Moleculares e Diagnóstico

Biomarkers for Pulmonary Effects Induced by In vivo Exposure to Cadmium-Doped Silica Nanoparticles

Abstract

Teresa Coccini, Cinzia Signorini and Elisa Roda

The study evaluated lung damages caused by in vivo exposure to silica nanoparticle doped with cadmium (SiNPs-Cd, 1 mg/rat) in terms of oxidative stress induction, apoptosis, and fibrosis, and assessed the validity of plasma F2-isoprostanes (F2-IsoPs) as marker of pulmonary insult. SiNPs-Cd effect was assessed 24 hr, 7 and 30 days post-intratracheal instillation compared to that caused by CdCl2 (400 μg/rat), or SiNPs (600 μg/rat) characterizing pulmonary superoxide dismutase (SOD1), cyclooxygenase type-2 (COX2) and collagen expression (by immunohistochemistry and TEM), and investigating apoptosis (TUNEL staining). Free and esterified F2- IsoPs were measured in lung and plasma by gas chromatography/negative ion chemical ionization tandem mass spectrometry (GC/NICI-MS/MS) analysis. Lung: SiNPs-Cd induced enhancement of SOD1 and COX2 immunoreactivity in a time-dependent manner (7<30 days). Total F2-IsoPs also increased 30 days post-exposure (46.7 ± 11 ng/g in SiNP-Cd vs. 32.8 ± 7.8 ng/g in control). Parallely, apoptosis enhanced as following SiNPs-Cd>CdCl2>SiNPs. A strong fibrotic response, i.e. interstitial type I collagen over-expression, was also observed starting at 7 days, particularly after SiNPs-Cd. Plasma: Pronounced elevation of free F2-IsoPs occurred (54.6 ± 2 vs. 28 ± 8 pg/ml in SiNPs-Cd andcontrol, respectively) already at day 7 lasting until day 30. In SiNPs-treated animals no changes were observed on oxidative stress parameters. The CdCl2 pulmonary response was milder than that found with SiNPs-Cd. The results indicate long-lasting tissue injury following SiNPs-Cd pulmonary exposure in rat and a role for plasma F2-IsoPs as a predictive indicator of nanoparticle-induced oxidative insult