Reactive oxygen species and lipid peroxyl radicals (ROS/LOO•)

Reactive oxygen species (ROS) and lipid peroxyl radicals are highly reactive chemical entities that play a critical role in cellular redox homeostasis and signaling. When produced in excess, these species target the polyunsaturated fatty acids within biological membranes, initiating a destructive chain reaction known as lipid peroxidation [1]. This process leads to the formation of toxic lipid hydroperoxides and reactive aldehydes, such as malondialdehyde, which can damage proteins and DNA [2]. The accumulation of lipid peroxyl radicals is a defining feature of ferroptosis, a non-apoptotic form of cell death linked to various pathological states including neurodegeneration and organ injury [3]. Consequently, these radicals are significant therapeutic targets in diseases characterized by oxidative stress, such as Amyotrophic Lateral Sclerosis (ALS) and ischemia-reperfusion injury [4]. Pharmacological strategies involve the use of radical-trapping antioxidants (RTAs) and scavengers, such as edaravone and alpha-tocopherol, which neutralize these species to prevent membrane degradation [5][6]. Effective targeting requires molecules with sufficient lipophilicity to access the hydrophobic core of the lipid bilayer where these radicals reside [1]. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920909/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617710/ [3] https://www.nature.com/articles/s41419-020-03007-3 [4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350122/ [5] https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209175s000lbl.pdf [6] https://pubmed.ncbi.nlm.nih.gov/21248165/

Other names

ROSLipid peroxyl radicalsMembrane lipid radicalsOxidative stress mediatorsLipid hydroperoxyl radicals

Radical scavenging and termination of lipid peroxidation chain reactions by donating hydrogen atoms or electrons to neutralize reactive species.