IntroductionChronic radiation proctitis (RP) is characterized by persistent inflammation and impaired tissue repair. This study investigates the potential of a metformin–butyrate (MeBu) combination to modulate radiation-induced senescence-associated changes in macrophages to mitigate chronic injury.Materials and methodsBALB/c mice received a 15 Gy fraction of rectal brachytherapy.
From weeks 4 to 8 post-irradiation, mice were treated with rectal enemas of metformin, butyrate, or the MeBu combination. Tissue histology (H&E and Masson’s Trichrome staining), macrophage polarization (iNOS/CD163) were evaluated.
Effects on senescence markers were analyzed in irradiated bone marrow–derived macrophages (BMDMs) using SA-β-gal staining and qPCR for p16 and p21. A composite Senescence Burden Index (SBI) was developed to integrate transcriptional senescence signals.ResultsMeBu treatment was associated with a reduction in mucosal fibrosis and a phenotypic shift in macrophages toward a more reparative M2-like profile (increased CD163/iNOS ratio).
In BMDMs, MeBu significantly reduced SA-β-Gal positivity and suppressed p21 expression (p = 0.0074), with a downward trend in p16 (p = 0.0568). The integrated SBI demonstrated that MeBu significantly attenuated the overall senescence burden compared to the irradiated group (p < 0.01).
Frontiers in Immunology published a clinical update in Infectious Disease on 02 Apr 2026.
The item focuses on Metformin and butyrate attenuate chronic radiation proctitis by alleviating inflammation and macrophage senescence.
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