2. Academic Validation
  3. Impaired GPX4 activity elicits ferroptosis in alveolar type II cells promoting PHMG-induced pulmonary fibrosis development

Impaired GPX4 activity elicits ferroptosis in alveolar type II cells promoting PHMG-induced pulmonary fibrosis development

  • Ecotoxicol Environ Saf. 2024 Aug:281:116680. doi: 10.1016/j.ecoenv.2024.116680.
Wanjun Zhang 1,  Zhaolong Sun 1,  Wenting Cheng 2,  Xin Li 2,  Jianzhong Zhang 2,  Yanting Li 2,  Haining Tan 3,  Xiaoya Ji 2,  Lin Zhang 4,  Jinglong Tang 5
Affiliations

Affiliations

  • 1 Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250001, China; Departmental of Occupational and Environmental Health, School of Public Health, Qingdao University, Qingdao 266071, China.
  • 2 Departmental of Occupational and Environmental Health, School of Public Health, Qingdao University, Qingdao 266071, China.
  • 3 Research Center for Intelligent Computing Systems, Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China.
  • 4 Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250001, China; Departmental of Occupational and Environmental Health, School of Public Health, Qingdao University, Qingdao 266071, China. Electronic address: zhanglin8901@sdu.edu.cn.
  • 5 Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan 250001, China; Departmental of Occupational and Environmental Health, School of Public Health, Qingdao University, Qingdao 266071, China. Electronic address: tangjinglong@qdu.edu.cn.
PMID: 38964057 DOI: 10.1016/j.ecoenv.2024.116680
Abstract

Inhaling polyhexamethylene guanidine (PHMG) aerosol, a broad-spectrum disinfectant, can lead to severe pulmonary fibrosis. Ferroptosis, a form of programmed cell death triggered by iron-dependent lipid peroxidation, is believed to play a role in the chemical-induced pulmonary injury. This study aimed to investigate the mechanism of Ferroptosis in the progression of PHMG-induced pulmonary fibrosis. C57BL/6 J mice and the alveolar type II cell line MLE-12 were used to evaluate the toxicity of PHMG in vivo and in vitro, respectively. The findings indicated that iron deposition was observed in PHMG induced pulmonary fibrosis mouse model and Ferroptosis related genes have changed after 8 weeks PHMG exposure. Additionally, there were disturbances in the antioxidant system and mitochondrial damage in MLE-12 cells following a 12-hour treatment with PHMG. Furthermore, the study observed an increase in lipid peroxidation and a decrease in GPX4 activity in MLE-12 cells after exposure to PHMG. Moreover, pretreatment with the Ferroptosis inhibitors Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) not only restored the antioxidant system and GPX4 activity but also mitigated lipid peroxidation. Current data exhibit the role of Ferroptosis pathway in PHMG-induced pulmonary fibrosis and provide a potential target for future treatment.

Keywords

Ferroptosis; GPX4 activity; Lipid peroxidation; Polyhexamethylene guanidine; Pulmonary fibrosis.

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