%20is%20a%20major%20complication%20of%20colorectal%20cancer%20radiotherapy.%20This%20study%20shows%20that%20nicotinamide%20riboside%20(NR)%20markedly%20reduces%20IR%20severity%20in%20mice,%20...){kind=link}
Nicotinamide Riboside Protects Against Radiation-Induced Intestinal Injury: Preclinical Findings
Synopsis
Radiation-induced intestinal injury (IR) is a major complication of colorectal cancer radiotherapy. This study shows that nicotinamide riboside (NR) markedly reduces IR severity in mice, improving weight loss, intestinal length, tissue histology, and gut microbiota balance. NR enhanced epithelial repair by increasing goblet cell density, crypt length, Ki-67 and ZO-1 expression, reducing ROS, and preserving mitochondrial structure. Mechanistically, NR activated SIRT1 and suppressed gasdermin E (GSDME)-mediated pyroptosis, a form of inflammatory cell death. Using IEC-specific Gsdme knockout mice and SIRT1 inhibition, the study confirmed that NR’s protective effects rely on SIRT1-dependent GSDME inhibition. Importantly, colorectal mucosa from radiotherapy patients showed elevated GSDME and reduced SIRT1, Ki-67, and ZO-1, mirroring the mouse findings. Overall, NR restores intestinal epithelial homeostasis and represents a promising therapeutic strategy for mitigating radiation-induced intestinal injury.
Journal
Journal of Translational Medicine