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.
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