Oxidized and oxidizable lipids

Oxidized and oxidizable lipids are a broad class of molecules central to oxidative stress and regulated cell death pathways, particularly ferroptosis (Yin et al., 2011, Chem Rev; Stockwell et al., 2017, Cell). Oxidizable lipids, primarily polyunsaturated fatty acids (PUFAs), contain bis-allylic hydrogens that are highly susceptible to abstraction by reactive oxygen species, initiating a self-propagating chain reaction known as lipid peroxidation (Yin et al., 2011, Chem Rev). This process generates reactive lipid hydroperoxides and electrophilic aldehydes, such as 4-hydroxynonenal (4-HNE), which can damage cellular membranes and modify proteins (Yin et al., 2011, Chem Rev; Bochkov et al., 2010, Nat Rev Drug Discov). Oxidized phospholipids (OxPL) and oxidized low-density lipoprotein (OxLDL) act as damage-associated molecular patterns (DAMPs), promoting inflammation in diseases like atherosclerosis and non-alcoholic steatohepatitis (NASH) (Bochkov et al., 2010, Nat Rev Drug Discov; Witztum & Lichtman, 2003, Nature). Therapeutic strategies include the use of radical-trapping antioxidants (RTAs) like ferrostatin-1 to terminate peroxidation chains and the administration of deuterated PUFAs (e.g., RT001) that are chemically reinforced to resist oxidative attack (Stockwell et al., 2017, Cell; Shchepinov, 2007, BioEssays). Neutralizing these species or preventing their formation is a major focus for treating neurodegenerative diseases and ischemia-reperfusion injury (Stockwell et al., 2017, Cell; Bochkov et al., 2010, Nat Rev Drug Discov).

Other names

Lipid peroxidesOxidized phospholipidsOxPLOxidized low-density lipoproteinOxLDLPolyunsaturated fatty acidsPUFAsLipid hydroperoxides

Inhibition of lipid peroxidation through radical trapping, enzymatic neutralization, or structural modification of lipid substrates (e.g., deuteration) to increase oxidative resistance.