Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder

Abstract

Radiation-induced intestinal injury is a common and critical complication of radiotherapy for pelvic or abdominal tumors, with limited therapeutic strategies and effectiveness. Sitagliptin, a dipeptidyl peptidase IV (DPP4) inhibitor, has previously been reported to alleviate total body irradiation- (TBI-) induced damage of hematopoietic system in mice, but its effect on radiation-induced intestinal injury remains unclear. In this study, we confirmed that Sitagliptin could not only protect mice from death and weight loss caused by whole abdominal irradiation (WAI) but also improve the morphological structure of intestine and the regeneration ability of enterocytes. In addition, Sitagliptin significantly inhibited the production of radiation-induced proinflammatory cytokines and reduced the number of apoptotic intestinal epithelial cells and γ-H2AX expression. In vitro, we demonstrated that Sitagliptin protected HIEC-6 cells from ionizing radiation, resulting in increased cell viability and reduced DNA damage. Mechanistically, the radiation protection of Sitagliptin might be related to the upregulation of NRF2 level and the decrease of NLRP3 inflammasome activity. Importantly, Sitagliptin significantly restored radiation-induced changes in bacterial composition. In conclusion, our results suggested that Sitagliptin could reduce WAI-induced intestinal injury in mice, which may provide novel therapeutic strategy for radiation-induced intestinal injury.

Medication adjustment of afatinib and combination therapy with sitagliptin for alleviating afatinib-induced diarrhea in rats

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Autophagy gene Atg7 regulates the development of radiation‐induced skin injury and fibrosis of skin

“…13 It is well known that radiation-induced injury can involve various tissues and organs. Given that our research group has a long-standing commitment to the search for occurrence and prevention of side effects related to radiotherapy, and some achievements have been made in the relevant field, [14][15][16][17][18] there is great interest in side effects of radiotherapy. However, the association between autophagy and radiation-induced skin injury has not yet been determined.…”

Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances

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