Original Research: Evaluation of pulmonary response to inhaled tungsten (IV) oxide nanoparticles in golden Syrian hamsters

Abstract

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.

The Interaction of Tungsten Dust with Human Skin Cells

“…Considering this increased concentration, the risk of inhalation or contamination with these nanoparticles is high. Increased tungsten use could lead to contamination of air, water, and soil near tungsten mines or industrial sites [13]. In speciality studies, exposure of W particles has been shown to have no adverse effect at a concentration of up to 100 μg/mL, and the toxic effect is significant at a concentration of at least 250 μg/ mL [1].…”

Design of an Inhalation Chamber and Metrology Assessment to Study Tungsten Aerosol Neurotoxic Effects

“…forms. Experimental studies have demonstrated an increase in inflammation and oxidative stress processes as well as histological impairments in rodent lungs after exposure of upper airways to tungsten (Roedel et al, 2012;Prajapati et al, 2017). Very recently, using two in vitro models, BEAS-2B cells and 3D human airway epithelium model, differential responses to tungsten were documented: epigenotoxic alterations and transient inflammatory response (George et al, 2019;Uboldi et al, 2019).…”

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

“…The broad use of MoO 3 NPs raises a concern of possible adverse health effects in humans as various metal nanoparticles such as tungsten oxide, cobalt oxide, lanthanum oxide, cerium oxide, and carbon nanotubes have been associated with accumulation in tissues and tissue injury. 6–10 Although respiratory exposure to MoO 3 NPs has not been thoroughly studied, the inhalation of Mo compounds has been shown to result in irritation to the respiratory tract, pulmonary hemorrhages, perivascular edema, and damage to the liver and kidneys. 11 A long-term study of occupational exposure to Mo fumes containing MoO 3 has indicated that concentrations between 1 and 19 mg/m 3 resulted in the development of pneumoconiosis.…”

“…16 Golden Syrian Hamsters have been used as models of lung diseases such as pulmonary fibrosis, emphysema, and acute lung injury. 6,17,18 More recently, this animal model has been used to study the sex differences following infection to SARS-CoV-2, along with the development of acute respiratory distress syndrome. 19,20…”