Selenium Attenuates Radiation Colitis by Regulating cGAS-STING Signaling

Area of Science:

• Oncology
• Radiotherapy
• Gastroenterology

Background:

• Radiation colitis is a frequent complication of pelvic radiotherapy with no effective clinical treatments.
• There is an urgent need for novel therapeutic agents to manage radiation-induced intestinal injury.

Purpose of the Study:

• To investigate the protective effects of selenium (Se) and selenium nanoparticles (SeNPs) against radiation colitis.
• To elucidate the underlying molecular mechanisms of SeNPs in mitigating radiation-induced intestinal damage.

Main Methods:

• Assessment of X-ray-induced apoptosis, cell cycle arrest, and inflammation in a radiation colitis model.
• Analysis of reactive oxygen species generation and DNA damage response.
• Investigation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-TBK1-IRF3 signaling pathway.
• Evaluation of selenoprotein expression (e.g., GPX4) and its impact on intestinal immunity and gut microbiota.

Main Results:

• Selenium, particularly SeNPs, demonstrated protective effects by inhibiting apoptosis, cell cycle arrest, and inflammation.
• SeNPs effectively balanced reactive oxygen species generation and restrained DNA damage response, reducing intestinal injury.
• SeNPs suppressed the cGAS-STING-TBK1-IRF3 pathway, blocking inflammatory cytokine (IL-6, TNF-α) transcription.
• In vivo SeNP treatment induced selenoprotein expression, regulated intestinal immunity, and modulated gut microbiota, attenuating radiation colitis.

Conclusions:

• Selenium nanoparticles represent a novel therapeutic strategy for radiation colitis.
• SeNPs exert protective effects through inducing selenoprotein expression and suppressing the cGAS-STING-TBK1-IRF3 cascade, thereby mitigating oxidative stress and inflammation.