Research progress on the hallmarks of radiation-induced intestinal injury: Mechanisms, biomarkers and therapeutic targets

Radiation-induced intestinal injury (RIII) is a major factor limiting the dose in abdominal and pelvic radiotherapy. This review summarizes our current understanding of RIII, focusing on its mechanisms, biomarkers, and potential treatment targets. Radiation directly induces DNA damage in intestinal epithelial cells and contributes to excessive reactive oxygen species (ROS), which together lead to increased apoptosis and decreased regeneration of intestinal stem cells (ISCs). An impaired antioxidant system also contributes to excessive ROS levels. Damage to ISCs results in decreased mucus production and compromised tight junctions, causing damage to the intestinal barrier. Epithelial cells impairment triggers ongoing inflammation, which promotes fibrogenesis and angiogenesis, processes involved in excessive wound healing during this damage. Endothelial cells experience DNA damage and ROS injury similar to that of epithelial cells. Intestinal vascular dysfunction, including increased permeability, ischemia, and angiogenesis, is involved throughout all stages of RIII. Additionally, dysbiosis of intestinal flora is characterized by reduced diversity, an overgrowth of conditional pathogens, and a decrease in probiotics. Current treatments for RIII include anti-inflammatory drugs, antibiotics, mucosal protective agents, and probiotics. Other therapies, such as anti-ferroptosis agents and targeted drugs, are still in preclinical studies. Traditional Chinese medicine, including decoctions, single herbs, or extracts, shows potential in treating RIII. The pathophysiology of RIII involves multiple dynamic steps, each with both harmful and protective aspects. Future research should delve deeper into these dual aspects of radiation-induced damage and its associated complications.