Pathophysiology
Clinical meaning
Oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds the capacity of endogenous antioxidant defense systems, resulting in oxidative damage to lipids, proteins, and DNA. ROS are chemically reactive molecules derived from molecular oxygen that include superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH-), and peroxynitrite (ONOO-). Under normal aerobic metabolism, the mitochondrial electron transport chain (ETC) is the primary endogenous source of ROS: approximately 1-2% of electrons leak from complexes I and III during oxidative phosphorylation, reducing molecular oxygen to superoxide. This basal ROS production serves important physiological signaling functions in cell proliferation, immune defense (respiratory burst in neutrophils), and vascular tone regulation. The cell maintains redox homeostasis through a multilayered antioxidant defense system. Enzymatic defenses include superoxide dismutase (SOD, which converts superoxide to H2O2), catalase (which converts H2O2 to water and oxygen in peroxisomes), and glutathione peroxidase (GPx, which reduces H2O2 and lipid hydroperoxides using reduced glutathione as a cofactor). Glutathione (GSH) is the most abundant intracellular antioxidant, present at millimolar concentrations; the ratio of reduced to oxidized glutathione (GSH:GSSG) is the primary indicator...