Abstract | BACKGROUND: METHODS: A lung ischemia-reperfusion model was established in wild-type and Nrf2-/- mice, and pulmonary epithelial cells were exposed to hypoxia/regeneration in vitro. We evaluated ferroptosis-related factors by western blotting, transmission electron microscopy, and fluorescence microscopy. To investigate the regulation of Nrf2 by salidroside, coimmunoprecipitation and luciferase reporter assays were used. Transwell assays were used to detect macrophage migration. RESULTS: The data indicated that salidroside postconditioning significantly reduced ferroptosis and alleviated lung ischemia-reperfusion injury in wild-type mice, as evidenced by improved histology and inflammation, reduced lipid peroxides and iron overload, and the induction of Nrf2, SLC7A11, and GPX4 expression. Salidroside activated Nrf2 signaling, resulting in Keap1-Nrf2 dissociation, nuclear translocation, and increased antioxidant-response element reporter activity. Sal consistently inhibited hypoxia/regeneration-induced pulmonary epithelial cell ferroptosis by activating the Nrf2 signaling pathway. Furthermore, ferroptotic cells recruited macrophages via CCL2, whereas salidroside lowered CCL2 expression and inhibited ferroptosis-induced macrophage chemotaxis in lung ischemia-reperfusion injury. Additionally, the antiferroptotic effects of salidroside against lung ischemia-reperfusion injury were eliminated in Nrf2-/- mice. CONCLUSIONS:
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Authors | Yun Wang, Zhe Chen, Jing Luo, Jing Zhang, A-Ming Sang, Zhen-Shun Cheng, Xin-Yi Li |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 115
Pg. 109731
(Feb 2023)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 36907990
(Publication Type: Journal Article)
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Copyright | Copyright © 2023 Elsevier B.V. All rights reserved. |
Chemical References |
- rhodioloside
- Kelch-Like ECH-Associated Protein 1
- NF-E2-Related Factor 2
- Antioxidants
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Topics |
- Animals
- Mice
- Ferroptosis
- Kelch-Like ECH-Associated Protein 1
- NF-E2-Related Factor 2
- Antioxidants
- Signal Transduction
- Reperfusion Injury
- Lung
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