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. 2025 Jan:744:151202.
doi: 10.1016/j.bbrc.2024.151202. Epub 2024 Dec 18.

Verapamil inhibits ferroptosis in septic acute lung injury by blocking L-type calcium channels

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Verapamil inhibits ferroptosis in septic acute lung injury by blocking L-type calcium channels

Hongru Li et al. Biochem Biophys Res Commun. 2025 Jan.

Abstract

Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), result from pulmonary edema and alveolar-capillary barrier disruption due to inflammation, often triggered by conditions like sepsis. Sepsis-induced ALI (SALI) involves extensive damage to vascular endothelium and alveolar epithelium, leading to respiratory failure. Our study explores ferroptosis, an iron-dependent cell death pathway, and calcium dysregulation in SALI. Elevated cytosolic calcium early in ferroptosis exacerbates lipid peroxidation and cellular damage. We investigated verapamil, a calcium channel blocker, and found it reduces calcium influx, alleviates iron overload, and decreases oxidative stress, protecting against ferroptosis-induced apoptosis in lung cells. These insights suggest targeting ferroptosis pathways, including calcium and iron homeostasis, may offer new therapeutic strategies for SALI, potentially improving outcomes in ALI/ARDS.

Keywords: Calcium; Ferroptosis; LTCC; SALI; Verapamil.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that might affect the research reported in this paper.

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