College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
Exp Biol Med (Maywood). 2022 Dec;247(23):2067-2080. doi: 10.1177/15353702221104033. Epub 2022 Jun 25.
Molybdenum trioxide nanoparticles (MoO 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 MoO NPs. Animals were separated into four groups: two control groups exposed to room air or aerosolized water and two treated groups exposed to aerosolized MoO NPs with a concentration of 5 mg/m 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 (* < 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, * < 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, * < 0.05), the levels of NLRP3 had a fold increase of 2.5 and 3.6 (T-1 * < 0.05, T-7 ** < 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, * < 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 MoO NPs may interrupt the autophagic flux and induce cytotoxicity and lung injury through pyroptosis cell death and activation of caspase-1.
三氧化钼纳米颗粒（MoO NPs）广泛应用于生物医药、农业和工程领域，可能会增加人类接触和不良健康影响的风险。本研究旨在评估吸入 MoO NPs 后导致细胞损伤和死亡的可能分子机制。动物分为四组：两组对照组分别暴露于室内空气或雾化水，两组实验组暴露于浓度为 5 mg/m NPs 的雾化 MoO NPs（每天 4 小时，共 8 天），并在暴露后进行为期 1 天（T-1）或 7 天（T-7）的恢复期。通过总细胞计数和分类细胞计数评估肺部毒性。T-1 组总细胞数、中性粒细胞和多核巨细胞增加，T-7 组淋巴细胞增加（* < 0.05）。为了评估毒性机制，评估了肺组织中 Beclin-1、轻链 3（LC3）-I/II、P-62、组织蛋白酶 B、NLRP3、ASC、半胱天冬酶-1、白细胞介素（IL）-1β和肿瘤坏死因子-α（TNF-α）的蛋白水平。免疫印迹分析表明，实验组 Beclin-1 分别增加了 1.4 倍和 1.8 倍（T-1 和 T-7，* < 0.05），但在任一组中 LC3-I/II 的蛋白水平均无变化。实验组中组织蛋白酶 B 的水平分别升高了 2.8 倍和 2.3 倍（T-1 和 T-7，* < 0.05），NLRP3 的水平升高了 2.5 倍和 3.6 倍（T-1 * < 0.05，T-7 ** < 0.01），半胱天冬酶-1 的水平升高了 3.8 倍和 3.0 倍（T-1 和 T-7，* < 0.05）。使用光镜和电子显微镜观察到形态学变化，显示气道上皮和肺泡发生改变，以及巨噬细胞内的颗粒内化。本研究结果可能表明，吸入 MoO NPs 可能会中断自噬流，并通过细胞焦亡和半胱天冬酶-1 的激活诱导细胞毒性和肺损伤。
