Reactive oxygen species and antioxidant defense systems (ROS/Antioxidant pathways)

Reactive oxygen species (ROS) are highly reactive oxygen-containing molecules, including superoxide radicals and hydrogen peroxide, produced primarily as byproducts of mitochondrial respiration and by specialized enzymes like NADPH oxidases [StatPearls, NBK545169]. The general antioxidant pathway comprises an integrated network of enzymatic defenses, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, alongside non-enzymatic antioxidants like glutathione [PubMed, PMC2763246]. Under physiological conditions, these pathways maintain redox homeostasis, which is critical for signal transduction and cellular survival [Nature, 582, 2020]. However, an imbalance resulting in excessive ROS leads to oxidative stress, causing cumulative damage to lipids, proteins, and DNA, a process central to the pathogenesis of neurodegenerative diseases, cardiovascular disorders, and cancer [NIH, 2022]. Pharmacological intervention typically targets these pathways by either directly scavenging ROS or, more commonly, by activating the Nrf2 (Nuclear factor erythroid 2-related factor 2) transcription factor to upregulate endogenous antioxidant gene expression [DrugBank, DB06451]. While promising, therapeutic modulation of these pathways faces challenges, as excessive suppression of ROS can interfere with essential physiological signaling processes, a phenomenon known as the antioxidant paradox [PubMed, 28239925].

Other names

Oxidative stress pathwaysRedox signaling pathwaysAntioxidant response element (ARE) pathwayRedox homeostasis

Direct scavenging of free radicals, induction of endogenous antioxidant enzymes via the Nrf2-KEAP1-ARE signaling axis, and inhibition of ROS-generating enzymes such as NADPH oxidase [PubMed, 28239925].