title: 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 (WO3NPs) in Golden Syrian Hamsters. Animals exposed to WO3NPs via inhalation were divided into three groups - control and two treatment groups exposed to either 5 or 10 mg/m3of aerosolized WO3NPs 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/m3, P < 0.05 and 10 mg/m3, P < 0.01, respectively), whereas levels of cathepsin B were 1.3 fold higher in lung tissue exposed to WO3NPs 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 WO3NPs may induce cytotoxicity, morphological changes, and lung injury via pyroptotic cell death pathway caused by activation of caspase-1.
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
authors.forename: Milankumar V
authors.initials: MV
authors.lastname: Prajapati
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
authors.forename: Olujoba O
authors.initials: OO
authors.lastname: Adebolu
authors.affiliation: Materials Science & Technology, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Morrow
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA cerretaj@stjohns.edu.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Cerreta
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D024243:HMGB1 Protein / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008647:Mesocricetus; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D010087:Oxides / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014414:Tungsten / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D024243:HMGB1 Protein; D058847:Inflammasomes; D010087:Oxides; D014409:Tumor Necrosis Factor-alpha; C511604:tungsten oxide; D014414:Tungsten
keywords: Tungsten oxide; inflammasome; inhalation; nanoparticles