Abstract
Although radiation therapy is a cornerstone of modern management of malignancies, various side effects are inevitably linked to abdominal and pelvic cancer after radiotherapy. Radiation-mediated gastrointestinal (GI) toxicity impairs the life quality of cancer survivors and even shortens their lifespan. Hydrogen has been shown to protect against tissue injuries caused by oxidative stress and excessive inflammation, but its effect on radiation-induced intestinal injury was previously unknown. In the present study, we found that oral gavage with hydrogen-water increased the survival rate and body weight of mice exposed to total abdominal irradiation (TAI); oral gavage with hydrogen-water was also associated with an improvement in GI tract function and the epithelial integrity of the small intestine. Mechanistically, microarray analysis revealed that hydrogen-water administration upregulated miR-1968-5p levels, thus resulting in parallel downregulation of MyD88 expression in the small intestine after TAI exposure. Additionally, high-throughput sequencing showed that hydrogen-water oral gavage resulted in retention of the TAI-shifted intestinal bacterial composition in mice. Collectively, our findings suggested that hydrogen-water might be used as a potential therapeutic to alleviate intestinal injury induced by radiotherapy for abdominal and pelvic cancer in preclinical settings.
Highlights
After the bone marrow, the gastrointestinal (GI) tract ranks as the second-most sensitive organ to irradiation injury during cancer therapy.[1]
We found that oral gavage with hydrogen-water increased the survival rate and body weight of mice exposed to total abdominal irradiation (TAI); oral gavage with hydrogen-water was associated with an improvement in GI tract function and the epithelial integrity of the small intestine
After exposure to 15 Gy TAI, the animal survival rate was decreased by 50% in the control vehicle group, but it was decreased by only 10% in animals receiving the hydrogen-water
Summary
The gastrointestinal (GI) tract ranks as the second-most sensitive organ to irradiation injury during cancer therapy.[1] During radiotherapy of abdominal and pelvic malignancies, ionizing radiation destroys the mucosal surface of the GI tract, leading to symptoms that may impair the course of treatment and even cause death.[2] Even for healthy populations, unexpected irradiation exposure leads to severe life-threatening intestinal injury.[3] irradiation-induced GI tract toxicity remains a conundrum that urgently requires effective therapy. Hydrogen has been considered an ideal therapeutic agent for a wide array of diseases, including cardiovascular, cerebrovascular, metabolic disorders and certain types of cancer.[6] Hydrogen can be administered in many different ways, among which hydrogen-water is a promising hydrogen usage, owing to its convenience and safety. It has been unknown whether hydrogen-water might confer protection against radiation-mediated intestinal toxicity in preclinical experimental settings
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