College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea; Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea; Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Ecotoxicol Environ Saf. 2024 Sep 15;283:116776. doi: 10.1016/j.ecoenv.2024.116776. Epub 2024 Jul 25.
Exposure to environmental heavy metals such as lead (Pb) and cadmium (Cd) is a global concern due to their widespread presence. However, the specific pulmonary effects of inhaled exposure, especially related to long-term effects, remain poorly understood. In this study, we developed a novel mouse model of Pb and Cd inhalation to mimic real-world conditions and investigate pulmonary effects. Mice were exposed to Pb and Cd inhalation for 6 months using a whole-body exposure system, resulting in decreased lung compliance and progression from emphysematous changes to fibrosis. In addition, the blood Pb/Cd levels of mice exposed to Pb/Cd for 6 months are like those of humans occupationally exposed to heavy metals. Histology revealed inflammation and collagen deposition. Transcriptomic analysis highlighted immune responses and macrophage activity in developing fibrosis. These results confirm an association between Pb/Cd exposure and emphysema and fibrosis, reflecting clinical findings. The study highlights the importance of long-term exposure assessment and time-course analysis for understanding Pb/Cd-induced lung disease. The relevance of the mouse model in replicating human exposure scenarios underscores its value in studying fibrosis and emphysema simultaneously. These findings provide a basis for targeted therapeutic interventions against heavy metal-induced lung injury.
暴露于环境重金属如铅(Pb)和镉(Cd)是一个全球性的关注问题,因为它们广泛存在。然而,吸入暴露的具体肺部效应,特别是与长期效应相关的,仍知之甚少。在这项研究中,我们开发了一种新的小鼠 Pb 和 Cd 吸入模型,以模拟真实世界的情况并研究肺部效应。小鼠使用全身暴露系统暴露于 Pb 和 Cd 吸入 6 个月,导致肺顺应性降低,并从气肿性改变进展为纤维化。此外,暴露于 Pb/Cd 6 个月的小鼠的血 Pb/Cd 水平类似于职业暴露于重金属的人类。组织学显示炎症和胶原沉积。转录组分析突出了免疫反应和巨噬细胞活性在纤维化形成中的作用。这些结果证实了 Pb/Cd 暴露与肺气肿和纤维化之间的关联,反映了临床发现。该研究强调了长期暴露评估和时间进程分析对于理解 Pb/Cd 引起的肺部疾病的重要性。在复制人类暴露情景方面,小鼠模型的重要性突显了其在同时研究纤维化和肺气肿方面的价值。这些发现为针对重金属引起的肺损伤的靶向治疗干预提供了基础。
Zhonghua Yu Fang Yi Xue Za Zhi. 2018-10-6
Environ Toxicol Pharmacol. 2017-7
Sci Total Environ. 2023-6-25
J Toxicol Environ Health A. 2018-3-28
J Korean Med Sci. 2015-3