Free iron ion and reactive oxygen species (Iron/ROS)

Free iron ions and reactive oxygen species (ROS) represent a critical chemical axis in cellular pathophysiology, primarily through their participation in the Fenton reaction (Winterbourn, 1995, PubMed: 7590364). In this process, labile ferrous iron (Fe2+) reacts with hydrogen peroxide to generate highly toxic hydroxyl radicals. These radicals initiate the non-enzymatic peroxidation of polyunsaturated fatty acids in cell membranes, a process central to ferroptosis (Dixon et al., 2012, Cell, 149(5):1060-72). Ferroptosis is a form of regulated cell death distinct from apoptosis and necrosis, often triggered by the loss of glutathione peroxidase 4 (GPX4) activity (Stockwell et al., 2017, Cell, 171(2):273-285). Pathological accumulation of free iron and ROS is implicated in a wide range of conditions, including neurodegenerative diseases like Parkinson's and Alzheimer's (Belaidi & Bush, 2016, J. Neurochem). Therapeutic strategies involve the use of iron chelators like Deferoxamine to sequester the labile iron pool or antioxidants to neutralize ROS (Cousins et al., 2021, Pharmaceuticals). While targeting these entities is effective in treating iron overload, maintaining the balance is crucial as both iron and ROS serve essential roles in normal physiological signaling (Halliwell & Gutteridge, 2015, Oxford University Press). Consequently, drugs targeting this axis must be carefully dosed to avoid interfering with essential metalloproteins and redox-sensitive pathways.

Other names

Labile iron poolLIPReactive oxygen speciesROSFerrous ironFerric ironOxidative stress mediatorsHydroxyl radicalSuperoxide

Iron chelation to prevent the Fenton reaction and direct scavenging of reactive oxygen species to inhibit lipid peroxidation and oxidative damage.