Unraveling Radiation Enteritis: Oxidative Stress as a Central Driver and Therapeutic Target

Radiation enteritis (RE) is a prevalent complication following abdominopelvic radiotherapy (RT), significantly compromising patients' quality of life. Oxidative stress extends beyond merely mediating early tissue injury; it acts as the central regulatory axis orchestrating sequential pathological transitions, encompassing epithelial damage, immune activation, chronic ischemia, and fibrotic remodeling.

RT-induced reactive oxygen species (ROS) burst provokes lipid peroxidation, mitochondrial dysfunction, programmed cell death, and epithelial barrier disruption. Subsequently, damage-associated molecular pattern release and microbial translocation propel immune-inflammatory amplification. Sustained ROS generation and ensuing inflammation further compromise the vascular endothelium, precipitating microcirculatory dysfunction and chronic hypoxia. Concurrently, barrier disruption and microbial dysbiosis form a feedback loop shifting sustained regenerative responses toward maladaptive repair, ultimately culminating in irreversible tissue remodeling.

Pathogenically, RE is not simply a consequence of ROS overload, but an ROS-driven continuum of tissue state transitions resulting in regenerative failure. Furthermore, a "redox paradox" emerges wherein ROS concurrently drive normal intestinal injury and mediate RT's tumoricidal efficacy. Currently, regenerative failure and this redox paradox remain inadequately integrated into clinical paradigms for patient stratification, interventional timing, and efficacy evaluation.

Future endeavors must prioritize precision redox therapeutics characterized by tissue specificity, temporal regulation, and dose-dependent modulation. Leveraging targeted delivery, phased interventions, and biomarkers will reconcile the conflicting demands of normal tissue radioprotection and tumor control, propelling the paradigm shift from broad-spectrum antioxidants toward precision redox medicine. Antioxid. Redox Signal. 00, 000-000.