Extensive industrial and military uses of tungsten have raised the possibilities of human occupational and environmental exposure to nanoparticles of this metal, with concomitant health concerns. The goal of this study was to investigate the potential mechanism of pulmonary toxicity associated with inhaled tungsten (IV) oxide nanoparticles (WO NPs) in Golden Syrian Hamsters. Animals exposed to WO NPs via inhalation were divided into three groups - control and two treatment groups exposed to either 5 or 10 mg/m of aerosolized WO NPs for 4 h/day for four days. A long-term exposure study (4 h/day for eight days) was also carried out using an additional three groups. Pulmonary toxicity assessed by examining changes in cell numbers, lactate dehydrogenase activity, alkaline phosphatase activity, total protein content, TNF-α, and HMGB1 levels in bronchoalveolar lavage fluids showed a significant difference when compared to control (P < 0.05). The molecular mechanism was established by assessing protein expression of cathepsin B, TXNIP, NLRP3, ASC, IL-1β and caspase-1. Western blot analysis indicated a 1.5 and 1.7 fold changes in NLRP3 in treatment groups (5 mg/m, P < 0.05 and 10 mg/m, P < 0.01, respectively), whereas levels of cathepsin B were 1.3 fold higher in lung tissue exposed to WO NPs suggesting activation of inflammasome pathway. Morphological changes studied using light and electron microscopy showed localization of nanoparticles and subsequent perturbation in airway epithelia, macrophages, and interstitial areas of alveolar structures. Results from the current study indicate that inhalation exposure to WO NPs may induce cytotoxicity, morphological changes, and lung injury via pyroptotic cell death pathway caused by activation of caspase-1.
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