Oxidative Stress: Signaling Pathways, Biological Functions, and Disease

Abstract

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single‐organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan‐organ diseases and interorgan communication remains insufficiently explored. This review integrates multidisciplinary evidence to elucidate the biological functions of OS in cellular signaling, homeostasis, and cross‐organ crosstalk. It systematically dissects OS‐driven molecular mechanisms and pathophysiological networks across 10 major organ systems, including the nervous, cardiovascular, oncological, hepatic, and renal systems. Furthermore, it critically examines OS‐related therapeutic targets, including antioxidant and ROS‐generating enzymes, and explores synergistic redox‐based therapeutic strategies. By moving beyond traditional single‐organ paradigms, this review constructs a holistic framework to decode the systemic impact of OS, offering novel insights into disease mechanisms and therapeutic innovations. Ultimately, it lays the foundation for precision medicine approaches aimed at mitigating OS‐driven diseases and improving multiorgan health outcomes.