Fluorofenidone alleviates cigarette smoke exposure-induced chronic lung injury by targeting ferroptosis
Abstract Chronic obstructive pulmonary disease (COPD) is a common condition that poses significant health risks to humans. Pulmonary interstitial fibrosis (PIF) often manifests in advanced stages of COPD. Fluorofenidone (AKF) has a wide range of pharmacological effects, including anti-fibrotic, anti...
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-83998-w |
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| author | Yuan Wu Binbin Li Yixuan Xuan Yu Jiang Jinping Chen Hong Liao Jihua Feng Jianfeng Zhang |
| author_facet | Yuan Wu Binbin Li Yixuan Xuan Yu Jiang Jinping Chen Hong Liao Jihua Feng Jianfeng Zhang |
| author_sort | Yuan Wu |
| collection | DOAJ |
| description | Abstract Chronic obstructive pulmonary disease (COPD) is a common condition that poses significant health risks to humans. Pulmonary interstitial fibrosis (PIF) often manifests in advanced stages of COPD. Fluorofenidone (AKF) has a wide range of pharmacological effects, including anti-fibrotic, antioxidant, and anti-inflammatory effects. Therefore, this study aimed to assess the role of AKF in lung injury and its underlying mechanisms. The COPD mice model was constructed by cigarette smoke (CS) combined with lipopolysaccharide (LPS) treatment. The effect of AKF on COPD mice was evaluated by lung injury, lipid peroxidation, inflammatory factors, and the expression of ferroptosis markers. Furthermore, the normal human bronchial epithelial cell line, Beas-2B, was used to verify the mechanism underlying the association between ferroptosis and inflammation. AKF attenuated the cigarette smoke (CS)/LPS-induced inflammatory response in the mouse lungs. Additionally, AKF attenuated the CS/LPS-induced fibrosis response in the mouse lungs. AKF inhibits ferroptosis in lung tissues of CS/LPS-exposed mice. Furthermore, AKF suppressed the inflammatory response and ferroptosis in CSE-treated BEAS-2B cells via NF-κB signaling pathway. AKF can function as a novel ferroptosis inhibitor by inhibiting NF-κB to inhibit airway inflammation and fibrosis, providing a scientific basis for the use of AKF to prevent the progression of COPD and pulmonary fibrosis. |
| format | Article |
| id | doaj-art-2f2f3e468b8b4f9cb1088f976737bf32 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-2f2f3e468b8b4f9cb1088f976737bf322025-01-05T12:29:42ZengNature PortfolioScientific Reports2045-23222024-12-0114111210.1038/s41598-024-83998-wFluorofenidone alleviates cigarette smoke exposure-induced chronic lung injury by targeting ferroptosisYuan Wu0Binbin Li1Yixuan Xuan2Yu Jiang3Jinping Chen4Hong Liao5Jihua Feng6Jianfeng Zhang7Department of General Practice, The Second Affiliated Hospital of Guangxi Medical UniversityDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Guangxi Medical UniversityDepartment of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical UniversityInstitute of Emergency Medicine, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics, Hunan Provincial People’s HospitalDepartment of General Medicine, Hunan Provincial People’s HospitalDepartment of General Medicine, Hunan Provincial People’s HospitalDepartment of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical UniversityDepartment of General Practice, The Second Affiliated Hospital of Guangxi Medical UniversityAbstract Chronic obstructive pulmonary disease (COPD) is a common condition that poses significant health risks to humans. Pulmonary interstitial fibrosis (PIF) often manifests in advanced stages of COPD. Fluorofenidone (AKF) has a wide range of pharmacological effects, including anti-fibrotic, antioxidant, and anti-inflammatory effects. Therefore, this study aimed to assess the role of AKF in lung injury and its underlying mechanisms. The COPD mice model was constructed by cigarette smoke (CS) combined with lipopolysaccharide (LPS) treatment. The effect of AKF on COPD mice was evaluated by lung injury, lipid peroxidation, inflammatory factors, and the expression of ferroptosis markers. Furthermore, the normal human bronchial epithelial cell line, Beas-2B, was used to verify the mechanism underlying the association between ferroptosis and inflammation. AKF attenuated the cigarette smoke (CS)/LPS-induced inflammatory response in the mouse lungs. Additionally, AKF attenuated the CS/LPS-induced fibrosis response in the mouse lungs. AKF inhibits ferroptosis in lung tissues of CS/LPS-exposed mice. Furthermore, AKF suppressed the inflammatory response and ferroptosis in CSE-treated BEAS-2B cells via NF-κB signaling pathway. AKF can function as a novel ferroptosis inhibitor by inhibiting NF-κB to inhibit airway inflammation and fibrosis, providing a scientific basis for the use of AKF to prevent the progression of COPD and pulmonary fibrosis.https://doi.org/10.1038/s41598-024-83998-wFluorofenidoneLung injuryLung fibrosisFerroptosisNF-κB |
| spellingShingle | Yuan Wu Binbin Li Yixuan Xuan Yu Jiang Jinping Chen Hong Liao Jihua Feng Jianfeng Zhang Fluorofenidone alleviates cigarette smoke exposure-induced chronic lung injury by targeting ferroptosis Scientific Reports Fluorofenidone Lung injury Lung fibrosis Ferroptosis NF-κB |
| title | Fluorofenidone alleviates cigarette smoke exposure-induced chronic lung injury by targeting ferroptosis |
| title_full | Fluorofenidone alleviates cigarette smoke exposure-induced chronic lung injury by targeting ferroptosis |
| title_fullStr | Fluorofenidone alleviates cigarette smoke exposure-induced chronic lung injury by targeting ferroptosis |
| title_full_unstemmed | Fluorofenidone alleviates cigarette smoke exposure-induced chronic lung injury by targeting ferroptosis |
| title_short | Fluorofenidone alleviates cigarette smoke exposure-induced chronic lung injury by targeting ferroptosis |
| title_sort | fluorofenidone alleviates cigarette smoke exposure induced chronic lung injury by targeting ferroptosis |
| topic | Fluorofenidone Lung injury Lung fibrosis Ferroptosis NF-κB |
| url | https://doi.org/10.1038/s41598-024-83998-w |
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