Targeting the ROS-ferroptosis axis: A clinical perspective on oxidative stress management in systemic lupus
Xiaoyan Xu1, Wenfeng Gao2, Lei Pang1
1Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University, 2428 Yuhe Road, Weifang 261031, China.
Abstract:
Systemic lupus erythematosus (SLE) is a classic autoimmune condition marked by inflammation in multiple organs and a malfunctioning immune system. Despite advances in immunosuppressive therapies, patients frequently experience relapses, organ damage, and significant quality-of-life impairment. Recent findings indicate that ferroptosis, a form of regulated cell death dependent on iron, has a substantial impact on the progression of lupus. However, the precise molecular interplay between reactive oxygen species (ROS) generation, iron metabolism dysregulation, and immune cell dysfunction in SLE remains incompletely understood. This review analyzes the ROS-ferroptosis axis in SLE, highlighting its role in promoting pathological immune responses and worsening tissue injury. It also discusses targeted therapies like iron chelators and GPX4 agonists, which show promise in preclinical models and early trials, identifies actionable targets, evaluates their translational potential for precision therapies, and bridges preclinical mechanisms with clinical applications to address unmet SLE management needs.
