Hydrogen peroxide and lipid hydroperoxides (H2O2/LOOH)

Hydrogen peroxide (H2O2) and lipid hydroperoxides (LOOH) are reactive oxygen species (ROS) that serve as critical mediators of oxidative stress and cellular signaling. H2O2 is a relatively stable ROS produced by superoxide dismutase (SOD) and various oxidases, functioning as a second messenger in pathways like MAPK and PI3K/Akt signaling (PMID: 28213294). Lipid hydroperoxides are derivatives of polyunsaturated fatty acids formed through enzymatic or non-enzymatic autoxidation, and their accumulation is the hallmark of ferroptosis, an iron-dependent form of regulated cell death (PMID: 22508501). In pathological states such as neurodegeneration, atherosclerosis, and cancer, the overproduction of these species overwhelms endogenous antioxidant defenses like glutathione peroxidase (GPx) and catalase. Pharmacological intervention typically involves the use of small-molecule antioxidants, radical scavengers, or GPx mimetics (e.g., Ebselen) to reduce these hydroperoxides to non-reactive alcohols or water, thereby preventing membrane damage and cell death (PMID: 15607313).

Other names

Reactive oxygen speciesROSHydroperoxidesLipid peroxidesOxidative stress markers

Drugs targeting these species primarily function through direct chemical neutralization, acting as reducing agents or radical scavengers that convert hydroperoxides into stable, non-toxic alcohols or water. Some agents act as catalytic mimetics of endogenous enzymes like glutathione peroxidase (GPx), utilizing cellular thiols to facilitate the reduction of H2O2 and lipid hydroperoxides (PMID: 8486331, PMID: 22508501).