Mechanisms of cell injury induced by inhaled molybdenum trioxide nanoparticles in Golden Syrian Hamsters

Abstract

Molybdenum trioxide nanoparticles (MoO3 NPs) are extensively used in the biomedical, agricultural, and engineering fields that may increase exposure and adverse health effects to the human population. The purpose of this study is to evaluate a possible molecular mechanism leading to cell damage and death following pulmonary exposure to inhaled MoO3 NPs. Animals were separated into four groups: two control groups exposed to room air or aerosolized water and two treated groups exposed to aerosolized MoO3 NPs with a concentration of 5 mg/m3 NPs (4 h/day for eight days) and given a one-day (T-1) or seven-day (T-7) recovery period post exposure. Pulmonary toxicity was evaluated with total and differential cell counts. Increases were seen in total cell numbers, neutrophils, and multinucleated macrophages in the T-1 group, with increases in lymphocytes in the T-7 group (* P < 0.05). To evaluate the mechanism of toxicity, protein levels of Beclin-1, light chain 3 (LC3)-I/II, P-62, cathepsin B, NLRP3, ASC, caspase-1, interleukin (IL)-1β, and tumor necrosis factor-α (TNF-α) were assessed in lung tissue. Immunoblot analyses indicated 1.4- and 1.8-fold increases in Beclin-1 in treated groups (T-1 and T-7, respectively, * P < 0.05), but no change in protein levels of LC3-I/II in either treated group. The levels of cathepsin B were 2.8- and 2.3-fold higher in treated lungs (T-1 and T-7, respectively, * P < 0.05), the levels of NLRP3 had a fold increase of 2.5 and 3.6 (T-1 * P < 0.05, T-7 ** P < 0.01, respectively), and the levels of caspase-1 indicated a 3.8- and 3.0-fold increase in treated lungs (T-1 and T-7, respectively, * P < 0.05). Morphological changes were studied using light and electron microscopy showing alterations to airway epithelium and the alveoli, along with particle internalization in macrophages. The results from this study may indicate that inhalation exposure to MoO3 NPs may interrupt the autophagic flux and induce cytotoxicity and lung injury through pyroptosis cell death and activation of caspase-1.

Distribution of molybdenum in soft tissues and blood of rats after intratracheal instillation of molybdenum(IV) sulfide nano- and microparticles

“…The initial histopathological lung damages were observed already at 10 mg/m 3 . In another study, Huber and Cerreta [ 37 ] reported an increase in the neutrophils and multinucleated macrophages in BAL fluid in hamsters after one day of inhalation of 5 mg Mo/m 3 , and lymphocytes after 7 days of exposure. The increase in neutrophils in BAL fluid was also observed in mice after inhalation of 90 mg Mo/m 3 [ 16 ].…”

The therapeutic bionanoscience interface

“…In this thematic issue, there are six mini-reviews and two original research articles targeting, toxicology, 1 pathogen and exosome detection, 2,3 spinal cord injury, 4 tissue scaffolds, 5 molecular barcoding, 6 RNA biology, 7 and bio-hybrid electronic devices 8 that bridge biology with nanotechnology and the bionanoscience interface.…”

“…In the area of nanotoxicology, Huber and Cerreta 1 demonstrate how inhaled nanoparticles exert their toxicological effect using a well-established model for lung diseases, Golden Syrian Hamsters. Exposure to molybdenum oxide nanoparticles that are commonly used as additives in a variety of industrial applications damages the lung by interfering with autophagy, activating inflammasome leading to lung inflammation, damage, and toxicity.…”