Reactive oxygen species and ROS-generating pathways (ROS)

Reactive oxygen species (ROS) are a group of highly reactive oxygen-containing molecules, including superoxide (O2•−), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH), which are generated as byproducts of aerobic metabolism or by specific enzymatic pathways like NADPH oxidases (NOX) and the mitochondrial electron transport chain (Sies & Jones, 2020). At physiological levels, ROS function as essential signaling molecules (redox signaling) that regulate processes such as cell proliferation, differentiation, and the immune response (Schieber & Chandel, 2014). However, an overproduction of ROS or a deficiency in antioxidant defenses leads to oxidative stress, resulting in oxidative damage to lipids, proteins, and DNA, which contributes to the pathogenesis of cancer, neurodegenerative disorders, and cardiovascular diseases (Pizzino et al., 2017). Therapeutic interventions targeting ROS include direct scavengers (antioxidants), inhibitors of ROS-generating enzymes like xanthine oxidase or NOX, and activators of endogenous antioxidant response elements like the Nrf2 pathway (Di Meo et al., 2016). While promising, targeting ROS presents challenges because complete suppression can interfere with vital homeostatic signaling and host defense mechanisms, such as the respiratory burst in neutrophils (Hamanaka & Chandel, 2010). Furthermore, the lack of specificity in many antioxidant therapies has led to mixed results in clinical trials, highlighting the need for more targeted approaches (Forman & Zhang, 2021).

Other names

Oxidative stress mediatorsOxygen radicalsPro-oxidantsReactive oxygen metabolitesReactive oxygen species

Drugs targeting this system act through direct scavenging of reactive species, inhibition of enzymatic sources such as NADPH oxidase or xanthine oxidase, or the induction of endogenous antioxidant defense systems via Nrf2 pathway activation (Di Meo et al., 2016; Pizzino et al., 2017).