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Radiotherapy destroys cancer cells and inevitably harms normal human tissues, causing delayed effects of acute radiation exposure (DEARE) and accelerating the aging process in most survivors. However, effective methods for preventing premature aging induced by ionizing radiation are lacking. In this study, the premature aging mice of DEARE model was established after 6 Gy total body irradiation (TBI). Then the therapeutic effects and mechanism of nicotinamide riboside on the premature aging mice were evaluated. The results showed that 6 Gy TBI induced premature aging of the hematopoietic system in mice. Nicotinamide riboside treatment reversed aging spleen phenotypes by inhibiting cellular senescence and ameliorated serum metabolism profiles. Further results demonstrated that nicotinamide riboside supplementation alleviated the myeloid bias of hematopoietic stem cells and temporarily restored the regenerative capacity of hematopoietic stem cells probably by mitigating the reactive oxygen species activated GCN2/eIF2α/ATF4 signaling pathway. The results of this study firstly indicate that nicotinamide riboside shows potential as a DEARE therapeutic agent for radiation‐exposed populations and patients who received radiotherapy. [ABSTRACT FROM AUTHOR]

Intestinal injuries caused by ionizing radiation (IR) are a major complication of radiotherapy. Ferrostatin-1 (Fer-1) exerts antioxidant and anti-inflammatory effects. We investigated the influence of Fer-1 on IR-induced intestinal damage and explored the possible mechanisms. IEC-6 cells were administrated with Fer-1 for 30 min and subsequently subjected to 9.0 Gy-irradiation. Flow cytometry, qPCR, and WB were used to detect changes. For in vivo experiments, Fer-1 was given intraperitoneally to mice at 1 h before and 24 h after 9.0 Gy total body irradiation (TBI) respectively. Three days after TBI, the small intestines were isolated for analysis. The diversity and composition of the gut microbiota were analyzed by 16S rRNA gene sequencing. In vitro, Fer-1 protected IEC-6 cells from IR injury by reducing the production of ROS and inhibiting both ferroptosis and apoptosis. In vivo, Fer-1 enhanced the survival rates of mice subjected to lethal doses of IR and restored intestinal structure and physiological function. Further investigation showed that Fer-1 protected IEC-6 cells and mice by inhibiting the p53-mediated apoptosis signaling pathway and restoring the gut-microbe balance. This study confirms that Fer-1 protects intestinal injuries through suppressing apoptosis and ferroptosis. [ABSTRACT FROM AUTHOR]

Radiation‐induced intestinal injury is one of the major side effects in patients receiving radiation therapy. There is no specific treatment for radiation enteritis in the clinic. We designed and synthesized a new compound named XH‐105, which is expected to cleave into polyphenol and aminothiol in vivo to mitigate radiation injury. In the following study, we describe the beneficial effects of XH‐105 against radiation‐induced intestinal injury. C57BL/6J mice were treated by gavage with XH‐105 1 hour before total body irradiation (TBI), and the survival rate was monitored. Histological changes were examined, and survival of Lgr5+ intestinal stem cells Ki67+ cells, villi+ enterocytes and lysozymes was determined by immunohistochemistry. DNA damage and cellular apoptosis in intestinal tissue were also evaluated. Compared to vehicle‐treated mice after TBI, XH‐105 treatment significantly enhanced the survival rate, attenuated structural damage of the small intestine, decreased the apoptotic rate, reduced DNA damage, maintained cell regeneration and promoted crypt proliferation and differentiation. XH‐105 also reduced the expression of Bax and p53 in the small intestine. These data suggest that XH‐105 is beneficial for the protection of radiation‐induced intestinal injury by inhibiting the p53‐dependent apoptosis signalling pathway. [ABSTRACT FROM AUTHOR]

• TRF restores the function of the hematopoietic system by inhibiting the NOX-4/ROS/p38 MAPK pathway. • TRF increases GSH-PX activity and promotes ROS clearance by promoting Nrf-2 nucleation. • TRF affects metabolism in plasma of total-body irradiated mice by regulating mTOR. Ionizing radiation (IR)-induced damage to the hematopoietic system is a prominent symptom following exposure to total body irradiation (TBI). The exploration of strategies aimed at to mitigating radiation-induced hematopoietic damage assumes paramount importance. Time-restricted feeding (TRF) has garnered attention for its beneficial effects in various diseases. In this study, we evaluated the preventive effects of TRF on TBI-induced hematopoietic damage. The results suggested that TRF significantly enhanced the proportion and function of hematopoietic stem cells in mice exposed to 4 Gy TBI. These effects might be attributed to the inhibition of the NOX-4/ROS/p38 MAPK pathway in hematopoietic stem cells. TRF also influenced the expression of nuclear factor erythroid2-related factor 2 and increased glutathione peroxidase activity, thereby promoting the clearance of reactive oxygen species. Furthermore, TRF alleviated aberrations in plasma metabolism by inhibiting the mammalian target of rapamycin. These findings suggest that TRF may represent a novel approach to preventing hematopoietic radiation damage. [ABSTRACT FROM AUTHOR]

Damage to the hematopoietic system and functional inhibition are severe consequences of radiation exposure. In this study, we have investigated the effect of empagliflozin on radiation-induced hematopoietic damage, with the aim of providing new preventive approach to such injuries. Mice were given 4 Gy total body irradiation (TBI) 1 h after the oral administration of empagliflozin, followed by the continuous administration of the same dose of empagliflozin for 6d, and then sacrificed on the 10th day after irradiation. The reactive oxygen species (ROS) levels in hematopoietic cells and their regulatory mechanisms were also been investigated. Colony forming unit granulocyte macrophage assay and bone marrow transplantation assays were performed to detect the function of the bone marrow cells. Empagliflozin increased the cell viability, reduced ROS levels, and attenuated apoptosis in vitro after the bone marrow cells were exposed to 1 Gy radiation. Empagliflozin significantly attenuated ionizing radiation injuries to the hematopoietic system, increased the peripheral blood cell count, and enhanced the proportion and function of hematopoietic stem cells in mice exposed to 4 Gy TBI. These effects may be related to the NOX-4/ROS/p38 pathway-mediated suppression of MAPK in hematopoietic stem cells. Empagliflozin also influenced the expression of Nrf-2 and increased glutathione peroxidase activity, thereby promoting the clearance of reactive oxygen species. Furthermore, empagliflozin mitigated metabolic abnormalities by inhibiting the mammalian target of rapamycin. Our study has demonstrated that empagliflozin can reduce radiation-induced injury in hematopoietic stem cells. This finding suggests that empagliflozin is a promising novel agent for preventing radiation-induced damage to the hematopoietic system. [Display omitted] • Empagliflozin protects the cell viability, reduces the level of ROS and apoptosis of irradiated BM cells • Empagliflozin restores the function of the hematopoietic system by inhibiting the NOX-4/ROS/p38 MAPK pathway • Empagliflozin augments GSH-Px activity and promotes Nrf-2 nucleation • Empagliflozin may affect glucose metabolism by regulating mTOR expression [ABSTRACT FROM AUTHOR]