Oxidative stress and lipid peroxidation pathways (OS/LPO)

Lipid peroxidation and oxidative stress pathways represent a complex network of biochemical reactions involving the production and neutralization of reactive oxygen species (ROS) and reactive nitrogen species (RNS) [4, 9]. Oxidative stress occurs when the balance between the production of these reactive species and the body's antioxidant defense mechanisms is disrupted, leading to damage of cellular components such as lipids, proteins, and DNA [6, 13]. Lipid peroxidation specifically refers to the oxidative degradation of lipids, particularly polyunsaturated fatty acids in cell membranes, which can lead to membrane instability and the formation of toxic byproducts like malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) [2, 3, 5]. These pathways play a critical role in the pathogenesis of numerous conditions, including neurodegenerative diseases, cardiovascular disorders, and cancer [1, 10]. While not a single molecular target, various enzymes and proteins within these pathways, such as glutathione peroxidase 4 (GPX4) and NADPH oxidase (NOX), are actively pursued as therapeutic targets to modulate redox balance and prevent cell death modalities like ferroptosis [7, 12]. Drugs targeting these pathways often act as direct antioxidants, ROS scavengers, or modulators of endogenous defense systems like the NRF2 pathway [4, 14].

Other names

Oxidative stressLipid peroxidationROS-mediated damageRedox stressLipid autoxidationReactive oxygen species signaling

Antioxidant activity, scavenging of reactive oxygen species (ROS), inhibition of lipid radical formation (chain-breaking), induction of endogenous antioxidant enzymes via NRF2 activation, or chelation of transition metals to prevent Fenton chemistry.