Mannose Ameliorates Radiation-Induced Intestinal Injury in Mice via Preventing Mitochondrial Dysfunction

Area of Science:

• Biochemistry
• Radiology
• Cell Biology

Background:

• Radiation-induced intestinal injury (RIII) is a debilitating side effect of radiotherapy, with no approved preventative or therapeutic agents.
• Current treatments for RIII are limited, impacting patient quality of life and potentially requiring radiotherapy cessation.

Purpose of the Study:

• To investigate the protective effects of mannose against RIII.
• To elucidate the underlying mechanisms of mannose's action in mitigating radiation damage.
• To identify mannose as a potential therapeutic agent for RIII.

Main Methods:

• Mice were administered mannose intraperitoneally at specific intervals before lethal irradiation.
• Assessed survival rates, crypt cell apoptosis, epithelial barrier integrity, inflammation, and crypt regeneration.
• Evaluated intestinal stem cell survival in vitro and in vivo.
• Investigated mannose's effects on mitochondrial homeostasis, oxidative stress, and DNA double-strand break repair.
• Assessed mannose's impact on colorectal tumor cell radiosensitivity.

Main Results:

• Mannose pretreatment increased mouse survival rates from 0% to 50% after lethal irradiation.
• Mannose significantly reduced crypt cell apoptosis, preserved epithelial barrier integrity, attenuated inflammation, and enhanced crypt regeneration.
• Mannose enhanced intestinal stem cell survival, maintained mitochondrial homeostasis, alleviated oxidative stress, and facilitated DNA double-strand break repair.
• Preliminary data showed mannose did not affect tumor cell radiosensitivity.

Conclusions:

• Mannose demonstrates significant protective effects against radiation-induced intestinal injury.
• Mannose acts by protecting intestinal stem cells, preserving barrier function, and promoting DNA repair.
• With low toxicity and availability, mannose is a promising strategy for RIII prevention and treatment.