Oxidative stress and lipid peroxidation (OS/LPO)

Oxidative stress represents a systemic imbalance where the production of reactive oxygen species (ROS) exceeds the capacity of biological systems to detoxify these reactive intermediates or repair the resulting damage (StatPearls, 2023). Lipid peroxidation is a hallmark of oxidative stress, specifically referring to the oxidative degradation of lipids where free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage and the formation of reactive aldehydes like 4-hydroxynonenal (PubMed, 2021). This biochemical cascade plays a critical role in the pathogenesis of numerous conditions, including cardiovascular diseases, neurodegenerative disorders like Alzheimer's, and cancer (NIH, 2022). In the context of drug development, this process is targeted through antioxidants, iron chelators, and Nrf2 activators which aim to mitigate cellular injury and prevent ferroptosis, an iron-dependent form of cell death (Nature, 2012). However, therapeutic intervention is complex because low levels of ROS are essential for normal physiological signaling, leading to a narrow therapeutic window for many redox-active drugs (Frontiers in Pharmacology, 2020).

Other names

Oxidative stress / lipid peroxidationReactive oxygen species damageOxidative damageFree radical-mediated lipid peroxidationRedox imbalance

Drugs targeting this process typically act by scavenging reactive oxygen species (ROS), activating the Nrf2-mediated antioxidant response, chelating catalytic metal ions like iron, or inhibiting enzymes such as lipoxygenases that propagate lipid peroxidation.