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

MARIANA GARCES; MAGNANI NATALIA; MARCHINI TIMOTEO; CACERES LOURDES; GUAGLIANONE ALEJANDRO; MEBERT ANDREA; TESAN FIORELLA; SALGUEIRO JIMENA; ZUBILLAGA MARCELA; DESIMONE MARTÍN; EVELSON PABLO

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Nanotechnology involves the manipulation and application of particles having at least one dimension smaller than 100 nm long. In vitro and in vivo toxicological studies suggest that nanoparticles are able to generate reactive oxygen species (ROS), leading to the release of proinflammatory mediators and oxidative stress. Transition metals, such as Ni (II), can be associate to nanoparticles (NP) and might be involved in the toxicological processes triggered by particulate matter inhalation. The aim of this work was to synthesize and characterize NP doped with Ni (II), and to study its biodistribution and mitochondrial alterations. 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 after 1 h. 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% at 3 h. NPs redox potential was evaluated as the inhibition of H2O2 production by the glucose/glucose oxidase system and EPR.Ni-NP was able to significantly inhibit H2O2 production by 43% at 45μg Ni/mL and 24%, 22.5 μg Ni/mL. A signal corresponding to OH generated from NP, NP-Ni and Ni (II) was observed in the EPR spectrum. NP were labeled with 99mTc; biodistribution studies showed that NPs mostly remain in lung (79%), while 18% were in stomach and 1% remained in the injection point. Scintigraphy imaging confirmed these results. Ni content in lung, heart, and plasma showed that Ni accumulates mostly in the lung (p