Oxidative stress and inflammation pathways

Oxidative stress and inflammation pathways represent a complex, interconnected network of biological processes that maintain cellular homeostasis and respond to injury. Oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds the capacity of antioxidant defense systems, leading to macromolecular damage (Sies & Jones, 2020, Nature Reviews Molecular Cell Biology). This state frequently triggers inflammatory signaling through the activation of redox-sensitive transcription factors such as NF-κB, which in turn promotes the release of pro-inflammatory cytokines (Morgan & Liu, 2011, Cell Research). Conversely, chronic inflammation sustains oxidative stress by recruiting immune cells that generate ROS via enzymes like NADPH oxidase, creating a self-perpetuating cycle (Mittal et al., 2014, Antioxidants & Redox Signaling). This axis is a central driver in the pathogenesis of numerous chronic conditions, including atherosclerosis, neurodegeneration, and metabolic syndrome (Furman et al., 2019, Nature Medicine). Therapeutic strategies often focus on specific molecular nodes within these pathways, such as the Nrf2-Keap1 system for antioxidant induction or the NLRP3 inflammasome for inflammatory control, to restore physiological balance (Cuadrado et al., 2019, Nature Reviews Drug Discovery).

Other names

Redox-inflammatory signalingOxidative-inflammatory axisPro-oxidant and pro-inflammatory pathways

Pharmacological intervention in these pathways involves the activation of endogenous antioxidant defenses, primarily through the Nrf2/ARE signaling axis, or the inhibition of pro-inflammatory mediators such as NF-κB, COX-2, and various cytokines (TNF-α, IL-1β, IL-6). Some agents act as direct scavengers of reactive oxygen species (ROS), while others inhibit ROS-generating enzymes like NADPH oxidase (NOX) or xanthine oxidase to prevent oxidative damage and subsequent inflammatory recruitment (Mittal et al., 2014, Antioxidants & Redox Signaling; Cuadrado et al., 2019, Nature Reviews Drug Discovery).