Pharmacological strategies for intestinal ischemia–reperfusion injury: mechanisms and therapeutic advances

Intestinal ischemia–reperfusion injury is a life-threatening complication of mesenteric ischemia, shock, major surgery, and transplantation. Reperfusion triggers oxidative stress, inflammation, barrier failure, microcirculatory dysfunction, and regulated cell death, leading to mucosal and remote-organ injury. This narrative review summarizes pharmacological strategies targeting oxidative injury, excessive inflammation, dysregulated cell death, and drug delivery, while considering experimental models, administration protocols, and translational feasibility. Thiol compounds, polyphenols, melatonin, SIRT-axis modulators, anti-inflammatory agents, ferroptosis and autophagy modulators, and targeted delivery platforms show therapeutic potential; however, most evidence derives from heterogeneous animal models using prophylactic or peri-reperfusion dosing, and clinical evidence remains very limited. Future studies should use clinically realistic treatment windows, standardized models and outcomes, and rational multimodal regimens.