2. Academic Validation
  3. Tempol suppresses ferroptosis and relieves chronic intermittent hypoxia-induced lung injury through the inhibition of TLR4 and activation of the Nrf2/GSH axis

Tempol suppresses ferroptosis and relieves chronic intermittent hypoxia-induced lung injury through the inhibition of TLR4 and activation of the Nrf2/GSH axis

  • Tissue Cell. 2026 Feb:98:103225. doi: 10.1016/j.tice.2025.103225.
Ran Li 1,  Ruiting Qin 2,  Zhijuan Liu 1,  Xiaojie He 1,  Dan Li 2,  Li Ai 3
Affiliations

Affiliations

  • 1 Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.
  • 2 Kunming Medical University, Kunming, Yunnan 650500, China.
  • 3 Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China. Electronic address: [email protected].
PMID: 41232311 DOI: 10.1016/j.tice.2025.103225
Abstract

Background: Chronic intermittent hypoxia (CIH) is a typical feature of obstructive sleep apnea (OSA), and CIH exposure can lead to the development of lung injury (LI). While tempol can be used to treat CIH-induced LI, its regulatory mechanism remains unclear. Therefore, the present study aimed to investigate the potential mechanism through which tempol improves the progression of CIH-induced LI.

Methods: In vitro and in vivo CIH-associated LI models were constructed using intermittent hypoxia (IH)-induced BEAS-2B cells and C57BL/6 mice. Cell viability was determined via the CCK-8 assay, and changes in related proteins were detected via Western blot analysis. The levels of Fe2 + , malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were detected via kits, and the level of Reactive Oxygen Species (ROS) was detected via fluorescence microscopy and flow cytometry. Lung tissue injury was evaluated by hematoxylin and eosin (HE) staining and Masson's trichrome staining.

Results: After IH induction, the levels of ferroptosis-related indicators (GPX4, FTH1, and SLC7A11), SOD and GSH were decreased in BEAS-2B cells and mouse lung tissues, whereas the levels of Fe2+, ROS and MDA were increased in BEAS-2B cells and mouse lung tissues. In addition, IH decreased BEAS-2B cell viability and aggravated lung tissue damage and fibrosis in mice. The addition of the Fer-1 Ferroptosis inhibitor or tempol weakened the effects of IH, indicating that tempol treatment improved the progression of CIH-induced LI through the inhibition of Ferroptosis. Mechanistically, tempol activated the Nrf2/GSH signaling axis through suppressing TLR4 expression, thereby inhibiting Ferroptosis and improving CIH-induced LI.

Conclusion: Tempol promotes Nrf2/GSH signaling through suppressing TLR4 expression, thereby inhibiting Ferroptosis and alleviating CIH-induced LI.

Keywords

Chronic intermittent hypoxia; Ferroptosis; Lung injury; Obstructive sleep apnea; TLR4/Nrf2/GSH; Tempol.

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