Investigation into the pulmonary inflammopathology of exposure to nickel oxide nanoparticles in mice.

We investigated the effects of nickel oxide nanoparticles (NiONPs) on the pulmonary inflammopathology. NiONPs were intratracheally installed into mice, and lung injury and inflammation were evaluated between 1 and 28 days. NiONPs caused significant increases in LDH, total protein, and IL-6 and a decrease in IL-10 in the BALF and increases in 8-OHdG and caspase-3 in lung tissues at 24 h. Airway inflammation was present in a dose-dependent manner from the upper to lower airways at 24 h of exposure as analyzed by SPECT. Lung parenchyma inflammation and small airway inflammation were observed by CT after NiONP exposure. 8-OHdG in lung tissues had increased with formation of fibrosis at 28 days. Focal adhesion was the most important pathways identified at 24 h as determined by protemics, whereas glutathione metabolism was the most important identified at 28 days. Our results demonstrated the pulmonary inflammopathology caused by NiONPs based on image-to-biochemical approaches.

Pulmonary pathobiology induced by zinc oxide nanoparticles in mice: A 24-hour and 28-day follow-up study.

Inhaled zinc oxide nanoparticles (ZnONPs) have high deposition rates in the alveolar region of the lungs; however, the adverse health effects of ZnONPs on the respiratory system are unclear. Herein, pathobiological responses of the respiratory system of mice that received intratracheal administration of ZnONPs were investigated by a combination of molecular and imaging (SPECT and CT) approaches. Also, normal BEAS-2B and adenocarcinoma A549 cells were used to confirm the results in mice. First, female BALB/c mice were administrated a series of doses of 20-nm ZnONPs and were compared to the phosphate-buffered saline control for 24-h and 28-day follow-up observations. Field emission-scanning electron microscopy and an energy-dispersive X-ray microanalysis were first used to characterize ZnONPs. After 24h, instilled ZnONPs had caused significant increases in lactic dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and the p63 tumor marker in lung tissues (p<0.05). Airway inflammation was present in a dose-dependent manner from the upper to the lower airway as analyzed by SPECT. After 28days, p63 had significantly increased due to ZnONP exposure in lung tissues (p<0.05). Pulmonary inflammatory infiltration mainly occurred in the left and right subsegments of the secondary bronchial bifurcation as observed by CT. A significant increase in p63 and decrease in TTF1 levels were observed in BEAS-2B cells by ZnONP (p<0.05), but not in A549 cells. Our results demonstrated that regional lung inflammation occurred with ZnONP exposure. We also showed that p63 was consistently overexpressed due to ZnONP exposure in vivo and in vitro. This work provides unique findings on the p63 response and the pathobiology in response to ZnONPs, which could be important to the study of pulmonary toxicity and repair.