Oxidative Stress as a Driver of Rheumatoid Arthritis: Mechanisms, Clinical Biomarkers, and Therapeutic Targeting

Abstract

This review focuses on the critical role of reactive oxygen species (ROS) in the pathogenesis of rheumatoid arthritis (RA) and explores potential therapeutic strategies targeting oxidative stress. ROS, including free radicals and non-radical species, are generated as byproducts of normal metabolic processes, but their excessive production leads to oxidative stress, contributing to inflammation and joint destruction in RA. We discuss mechanisms by which ROS drive synovial inflammation, activate immune cells, and modulate key transcription factors like NF-κB and Nrf2, enhancing the inflammatory response. The review highlights the significance of lipid peroxidation and oxidative damage markers, such as malondialdehyde and 8-hydroxy-2-deoxyguanosine, in RA pathology. Additionally, we examine various antioxidant strategies, including the application of natural compounds and mitochondrial-targeted therapies, aimed at mitigating oxidative stress. By addressing the inflammatory cycle perpetuated by ROS, this article underscores the potential of antioxidant therapies to alleviate RA symptoms and slow disease progression, paving the way for novel treatment approaches in clinical practice.