期刊
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
卷 229, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2021.113094
关键词
DNA damage; eIF2 alpha; Stress granules; Polyhexamethylene guanidine phosphate; Lung organoids; Pulmonary fibrosis
资金
- Korea Environment Industry & Technology Institute (KEITI) through the Environment Health Action Program [2018001360003]
- Chungnam National University
- Korea Institute of Toxicology [1711133839]
- Technology Innovation Program - Ministry of Trade, Industry Energy [20009350]
The study investigated the impact of PHMG-p on human lung tissue models under oxidative stress and viral infection, revealing that PHMG-p induced SG formation and severe lung toxicity. Evaluation of toxicity under stressful conditions is crucial for accurately predicting the potential effects of chemicals on the respiratory tract.
Polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, is known to cause lung toxicity, including inflammation and pulmonary fibrosis. In this study, we aimed to investigate the effect of PHMG-p on human lung tissue models (2D epithelial cells and 3D organoids) under conditions of oxidative stress and viral infection. The effect of PHMG-p was studied by evaluating the formation of stress granules (SGs), which play a pivotal role in cellular adaptation to various stress conditions. Under oxidative stress and respiratory syncytial virus (RSV) infection, exposure to PHMG-p remarkably increased eIF2a phosphorylation, which is essential for SG-related signalling, and significantly increased SG formation. Furthermore, PHMG-p induced fibrotic gene expression and caused cell death due to severe DNA damage, which was further increased under oxidative stress and RSV infection, indicating that PHMG-p induces severe lung toxicity under stress conditions. Taken together, toxicity evaluation under various stressful conditions is necessary to accurately predict potential lung toxicity of chemicals affecting the respiratory tract.
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