Nicotinamide riboside alleviates ionizing radiation-induced intestinal senescence by alleviating oxidative damage and regulating intestinal metabolism,Journal of Advanced Research

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Nicotinamide riboside alleviates ionizing radiation-induced intestinal senescence by alleviating oxidative damage and regulating intestinal metabolism
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2024-07-17 , DOI: 10.1016/j.jare.2024.07.010
Tongpeng Yue ₁ , Yinping Dong ₁ , Qidong Huo ₁ , Wenxuan Li ₁ , Xinyue Wang ₁ , Shiyi Zhang ₁ , Huirong Fan ₁ , Xin Wu ₁ , Xin He ₁ , Yu Zhao ₁ , Deguan Li ₁

Affiliation

Introduction

The intestine, frequently subjected to pelvic or abdominal radiotherapy, is particularly vulnerable to delayed effects of acute radiation exposure (DEARE) owing to its high radiation sensitivity. Radiation-induced intestinal senescence, a result of DEARE, profoundly affects the well-being and quality of life of radiotherapy patients. However, targeted pharmaceutical interventions for radiation-induced senescence are currently scarce. Our findings showcase that nicotinamide riboside(NR) effectively alleviates radiation-induced intestinal senescence, offering crucial implications for utilizing NR as a pharmacological agent to combat intestinal DEARE.

Objectives

The aim of this study was to investigate the ability of NR to reduce radiation induced intestinal senescence and explore its related mechanisms.

Methods

Male C57BL/6J mice were randomly divided into CON, IR, and IR + NR groups. The mice in the IR and IR + NR groups were subjected to a 6.0 Gy γ-ray total body exposure. After 8 weeks, the mice in the IR + NR group received NR via gavage at a dose of 400 mg/kg/d for 21 days. Then the mice were used for sample collection.

Results

Our results demonstrate that NR can significantly mitigate radiation-induced intestinal senescence. Furthermore, our findings indicate that NR can mitigate oxidative damage, restore the normal function of intestinal stem cells, regulate the disruption of the intestinal symbiotic ecosystem and address metabolic abnormalities. In addition, the underlying mechanisms involve the activation of SIRT6, SIRT7 and the inhibition of the mTORC1 pathway by NR.

Conclusion

In conclusion, our results reveal the substantial inhibitory effects of NR on radiation-induced intestinal senescence. These findings offer valuable insights into the potential therapeutic use of NR as a pharmacological agent for alleviating intestinal DEARE.

中文翻译：

烟酰胺核苷通过减轻氧化损伤和调节肠道代谢来减轻电离辐射诱导的肠道衰老

介绍

肠道经常接受盆腔或腹部放疗，由于其高辐射敏感性，特别容易受到急性辐射暴露（DEARE）的延迟影响。DEARE 导致的放射诱导的肠道衰老严重影响放疗患者的健康状况和生活质量。然而，针对辐射诱导的衰老的靶向药物干预目前很少。我们的研究结果表明，烟酰胺核苷（NR）有效缓解辐射诱导的肠道衰老，为利用 NR 作为药理学试剂对抗肠道 DEARE 提供了重要意义。