Intestinal oxidative stress

Intestinal oxidative stress is a pathological condition characterized by an imbalance between the production of reactive oxygen and nitrogen species (ROS/RNS) and the body's ability to detoxify these reactive intermediates or repair the resulting damage [4, 10]. This state is a hallmark of gastrointestinal diseases, particularly inflammatory bowel disease (IBD), where excessive ROS production by infiltrating leukocytes and inflamed mucosa leads to lipid peroxidation, protein carbonylation, and DNA damage [15, 17]. These oxidative modifications compromise the integrity of the intestinal epithelial barrier, promote apoptosis, and sustain a chronic inflammatory cycle through the activation of redox-sensitive pathways such as NF-kappaB [4, 13]. While not a single molecular entity, it is a significant focus of drug development, with strategies ranging from direct antioxidant scavenging (e.g., mesalamine) to the pharmacological activation of the master antioxidant regulator Nrf2 [11, 15]. Biomarkers such as malondialdehyde (MDA) and glutathione (GSH) levels are frequently used to monitor disease activity and the efficacy of antioxidant interventions [1, 5, 15].

Other names

Intestinal redox imbalanceGastrointestinal oxidative stressOxidative gut injuryEnteric oxidative stress

The therapeutic modulation of intestinal oxidative stress involves the direct scavenging of reactive oxygen species (ROS), the pharmacological activation of the Nrf2 (Nuclear factor erythroid 2-related factor 2) antioxidant signaling pathway, and the inhibition of pro-inflammatory transcription factors like NF-kappaB. Additionally, agents may target specific ROS-generating enzymes such as NADPH oxidase 1 (NOX1) or inducible nitric oxide synthase (iNOS), while others aim to replenish endogenous antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPx) to restore mucosal homeostasis [3, 4, 11, 13, 16].