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

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.