Reactive oxygen species and oxidative stress systems (ROS/Oxidative Stress)

Reactive oxygen species (ROS) and oxidative stress systems encompass the complex network of pro-oxidant molecules and the endogenous antioxidant defenses that maintain cellular redox homeostasis. ROS, such as superoxide anions and hydrogen peroxide, are primarily generated as metabolic byproducts by mitochondria and enzymes like NADPH oxidases (NOX) and xanthine oxidase [1, 5]. While physiological levels of ROS are essential for critical signaling processes, including immune response and cell proliferation, an imbalance—termed oxidative stress—leads to the damaging oxidation of DNA, proteins, and lipids [1, 15]. This state is a hallmark of numerous pathologies, including cancer, neurodegenerative diseases like Parkinson's, and cardiovascular disorders [3, 9]. Therapeutic strategies aim to restore redox balance by scavenging radicals, inhibiting ROS-producing enzymes, or activating transcription factors like Nrf2 to boost protective enzymes [5, 8]. However, targeting these systems is clinically challenging due to the "antioxidant paradox," where over-suppression can cause reductive stress or inadvertently protect malignant cells from oxidative-based therapies [10, 11].

Other names

Oxidative stress pathwayRedox signaling systemAntioxidant defense systemReactive oxygen species networkRedox homeostasis system

Drugs targeting these systems act by scavenging free radicals, inhibiting ROS-generating enzymes such as NADPH oxidase (NOX) or xanthine oxidase (XO), or activating the Nrf2-Keap1 pathway to upregulate endogenous antioxidant defenses and restore redox balance [3, 5, 8].