Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Potential role of ferroptosis in sterile acute lung injury induced by a non-hypoxic ischemia-reperfusion insult

Articles in Press

Document Type : Original Article

Authors
Farzaneh Kianian 1, 2
Xiaoli Tian 1
Daisuke Maruyama 1
Arun Prakash 1
1 Department of Anesthesia and Perioperative Care, University of California, San Francisco, and San Francisco General Hospital, San Francisco, CA, USA
2 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
10.22038/ijbms.2026.92610.19992
Abstract
Objective(s): Ferroptosis, a regulated form of necrotic cell death, is implicated in the pathogenesis of hypoxic lung ischemia-reperfusion injury (LIRI). However, its role in non-hypoxic LIRI, which occurs in common clinical conditions such as trauma and pulmonary embolism, remains unclear. Given that ferroptosis has been implicated in sterile inflammation and lipid peroxidation is a hallmark of this process, this study aimed to investigate the potential role of ferroptosis in inflammatory responses during non-hypoxic LIRI.
Materials and Methods: Non-hypoxic LIRI was induced in C57BL/6 mice by occluding the left pulmonary artery for 1 hr, followed by 30 min of reperfusion. The treatment group received liproxstatin-1 (Lip-1; 10 mg/kg, IP) 1 hr before surgery. IL-6 levels in plasma and lung tissue were measured by ELISA. For the in vitro model, normal human bronchial epithelial (NHBE) cells were exposed to nutritional ischemia for 1 hr and then reperfused for 2 hr. Cells were pretreated with Lip-1 (200 nM) 12 hr before ischemia. CXCL1 release was measured by ELISA, and lipid reactive oxygen species (ROS) accumulation was assessed by BODIPY 581/591 C11 fluorescence.
Results: Non-hypoxic LIRI markedly increased IL-6 levels in plasma and lung tissue, as well as CXCL1 levels and lipid ROS accumulation in NHBE cells. Pretreatment with Lip-1 significantly reduced these inflammatory responses and lipid ROS accumulation compared with untreated LIRI.
Conclusion: Our findings suggest that ferroptosis-associated lipid peroxidation is associated with sterile inflammatory responses during non-hypoxic LIRI in both systemic and epithelial compartments. Lip-1 attenuated these responses, highlighting a potential strategy for non-hypoxic LIRI.
Keywords
Chemokine CXCL1
Inflammation
Interleukin-6
Lipid peroxidation
Reperfusion injury
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 14 July 2026