Acute exposure to nickel-doped nanoparticles: mechanisms underlying its effects

GARCÉS MARIANA; MAGNANI NATALIA; MARCHINI TIMOTEO; CACERES LOURDES; GUAGLIANONE ALEJANDRO; VICO TAMARA; MEBERT ANDREA; TESAN FIORELLA; SALGUEIRO JIMENA; ZUBILLAGA MARCELA; DESIMONE MARTÍN; SILVIA ALVAREZ; EVELSON PABLO

Congreso; International Congress of Translational Medicine; 2016

Increased use of nanomaterials has raised concerns about the potential for undesirable human health and environmental effects. In vitro and in vivo toxicological studies suggest that nanoparticles are able to generate reactive oxygen species (ROS) and the release of proinflammatory mediators. Transition metals, such as Ni (II), can be associate to nanoparticles (NP) and might be involved in the toxicological mechanisms triggered by nanoparticles inhalation. The aim of this work was to study the role of Ni present in NP in the adverse health effects observed after NP inhalation. Female Swiss mice (25 g) were intranasally instilled with a Ni-NP suspension (1 mg Ni/kg body weight), delivered in a single dose (control group: Si-NP). Samples were collected 1 hour after exposure. NP share comparable physicochemical properties with air pollution PM in size (NP-Si: 170 ± 2 nm; Ni-NP: 200 ± 20 nm) and shape, as assayed by TEM and SEM. Ni released from Ni-NP was less than 1% 1 hour after exposure. NPs redox potential was evaluated as the consumption of H2O2 generated by the glucose/glucose oxidase system. Ni-NPs were able to significantly decreased H2O2 levels by 43% at 45 μg Ni/mL. Biodistribution studies using 99mTc labeled NP showed that NPs remained mostly in the lung (79 ± 3 %). Scintigraphy imaging confirmed these results. Ni content determinated by atomic absorption in lung, heart, and plasma showed that Ni accumulates in the lung (p< 0.001 vs. Ni in heart and plasma). Regarding oxidative metabolism, in lung the Ni-NP group showed an increase in tissue O2 consumption (67%; p˂0.001), NADPH oxidase (Nox) activity (41%; p˂0.001) and mitochondrial H2O2 production (41 %; p