Mannose ameliorates radiation induced intestinal injury in mice via preventing mitochondrial dysfunction

Radiation-induced intestinal injury (RIII) severely compromises the quality of life in patients undergoing abdominal/pelvic radiotherapy and may necessitates treatment discontinuation. To date, there is no approved agent for the prevention or treatment of RIII. This study aims to clarify the protective effects of mannose on RIII and elucidate its mechanisms of action, in order to identify new safe and effective therapeutic agents and potential therapeutic targets for the prevention and treatment of RIII.Here, we report that mannose, a natural bioactive monosaccharide, significantly prolonged survival in mice subjected to lethal irradiation. Specifically, mannose pretreatment significantly blocked crypt cell apoptosis, preserved epithelial barrier integrity, attenuated intestinal inflammation and enhanced crypt regeneration. Additionally, mannose treatment enhanced the survival of intestinal stem cells both in vitro and in vivo following radiation exposure. We further confirmed that mannose maintains mitochondrial homeostasis and alleviates cellular oxidative stress. Moreover, mannose facilitated the repair of DNA double-strand breaks, thereby inhibiting aberrant mitosis after radiation exposure. Additionally, preliminary evidence indicates that mannose does not affect the radiosensitivity of colorectal tumor cells or azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal tumors in mice.