Reactive oxygen species and iron-mediated lipid peroxidation (ROS/LPO)

Reactive oxygen species (ROS), particularly hydroxyl radicals generated via the iron-dependent Fenton reaction, drive the process of lipid peroxidation, which involves the oxidative degradation of polyunsaturated fatty acids in cellular membranes [1, 3]. This biochemical cascade is the defining feature of ferroptosis, a form of regulated cell death distinct from apoptosis and necrosis [1, 2]. In the presence of catalytic ferrous iron (Fe2+), ROS initiate a chain reaction that produces lipid hydroperoxides, leading to the loss of membrane integrity and eventual cell lysis [2, 3]. This process plays a critical role in the pathogenesis of various conditions, including neurodegenerative diseases, organ ischemia-reperfusion injury, and certain types of cancer [2, 4]. Therapeutic strategies focus on neutralizing ROS with antioxidants, sequestering iron with chelators, or utilizing specialized small molecules like ferrostatins to halt the propagation of lipid radical signals [1, 5]. Monitoring biomarkers such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) is essential for evaluating the extent of oxidative damage in clinical and experimental settings [2, 3].

Other names

Ferroptosis pathwayOxidative lipid damageFenton reaction-mediated lipid peroxidationHydroxyl radical-induced peroxidation

Drugs targeting this process typically act by scavenging reactive oxygen species, chelating catalytic iron to prevent the Fenton reaction, or inhibiting the chain reaction of lipid autoxidation to prevent membrane damage and ferroptotic cell death.