The interplay of ferroptosis and oxidative stress mechanisms: a critical contributor to chronic obstructive pulmonary disease pathophysiology

Ferroptosis, a recently discovered iron-dependent regulated form of cell death, is characterised by lipid peroxidation and oxidative stress. Recent studies suggested that ferroptosis plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD), a progressive and irreversible lung disorder, marked by airflow limitation, emphysema, and chronic bronchitis. Cigarette smoke (CS), one of the prominent risk factors for COPD, is known to induce ferroptosis by generating reactive oxygen species (ROS), depleting antioxidant defences, such as glutathione and glutathione peroxidase 4, and disrupting iron homeostasis. These molecular disturbances lead to cell damage, alveolar destruction, and vascular dysfunction, contributing to disease progression and exacerbations. Ferroptosis is also linked with key COPD mechanisms, which are responsible for mitochondrial dysfunction, inflammation, pulmonary hypertension, and CS-induced irregular distribution of iron-binding proteins. A promising therapeutic strategy for mitigating COPD pathogenesis is targeting ferroptosis via iron chelators, lipid peroxide inhibitors, and antioxidant upregulation. Understanding the regulatory mechanisms governing ferroptosis in lung tissue damage could help identify novel biomarkers and effective treatment strategies. This review explores the mechanistic role of ferroptosis in COPD and uncovers the potential intervention methods that may improve clinical outcomes.