Lipid peroxyl radicals and ROS-driven lipid peroxidation chains in membrane polyunsaturated fatty acids (LOO•) (LOO•)

Lipid peroxyl radicals (LOO•) are highly reactive intermediates formed during the process of lipid peroxidation, specifically within membrane polyunsaturated fatty acids (PUFAs). This process is initiated by reactive oxygen species (ROS) or enzymes like lipoxygenases, leading to a self-propagating chain reaction that damages cellular membranes and produces toxic byproducts like malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) (Ayala et al., 2014, PMID: 24999379). These radicals are central to the mechanism of ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation (Dixon et al., 2012, PMID: 22559948). Targeting these radicals or the chain reaction itself is a major therapeutic strategy for neurodegenerative diseases, cardiovascular disorders, and ischemia-reperfusion injury (Gaschler & Stockwell, 2017, PMID: 28213274). Drugs such as radical-trapping antioxidants (RTAs) like Ferrostatin-1 and Liproxstatin-1, as well as natural antioxidants like Vitamin E, work by donating a hydrogen atom to the peroxyl radical, thereby terminating the destructive chain reaction (Zilka et al., 2017, PMID: 28112910). Additionally, the use of deuterated PUFAs (e.g., RT001) has emerged as a strategy to stabilize membranes against radical-driven damage by slowing the rate-limiting step of hydrogen abstraction (Shchepinov, 2011, PMID: 21314141).

Other names

Lipid peroxidationLipid peroxyl radicalsMembrane lipid peroxidationROS-driven lipid peroxidationLipid autoxidationLipid-derived radicals

Radical-trapping antioxidant (RTA) activity and chain-breaking inhibition of lipid autoxidation to terminate the propagation of lipid peroxidation.