Effect of spermidine on radiation-induced long-term bone marrow cell injury

Bowen Guan; Chengcheng Li; Yin Yang; Yanhua Lu; Yuhang Sun; Lulu Su; Guiying Shi; Lin Bai; Jiangning Liu; Aimin Meng

doi:10.1016/j.intimp.2022.109557

Effect of spermidine on radiation-induced long-term bone marrow cell injury

Int Immunopharmacol. 2023 Jan:114:109557. doi: 10.1016/j.intimp.2022.109557. Epub 2022 Dec 19.

Authors

Bowen Guan¹, Chengcheng Li², Yin Yang³, Yanhua Lu⁴, Yuhang Sun¹, Lulu Su⁵, Guiying Shi¹, Lin Bai¹, Jiangning Liu¹, Aimin Meng⁶

Affiliations

¹ NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model, National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing 100021, China.
² NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model, National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing 100021, China; Burning Rock Biotech, Guangzhou 510300, China.
³ NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model, National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing 100021, China; Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
⁴ NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model, National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing 100021, China; National Institute of Biological Sciences, Beijing 102206, China.
⁵ NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model, National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing 100021, China; Department of Oncology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450000, China.
⁶ NHC Key Laboratory of Human Disease Comparative Medicine, National Center of Technology Innovation for Animal Model, National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing 100021, China. Electronic address: ai_min_meng@126.com.

PMID: 36692947
DOI: 10.1016/j.intimp.2022.109557

Abstract

Objective: Spermidine, a natural polyamine, possesses anti-oxidant, autophagy-regulation, and anti-aging properties. Elevated levels of oxidative stress, which was mediated the senescence of hematopoietic stem cells (HSCs) induced by radiation exposure, may further contribute to long-term myelosuppression. Therefore, this study investigated the protective effect of spermidine on the long-term damage of the hematopoietic system caused by radiation exposure.

Methods: In vitro experiments, bone marrow mononuclear cells (BMMNCs) of C57BL/6 mice were isolated and incubated with 5 mM spermidine for 30 min, then irradiated by 2 Gy X ray. The survival rate, proliferation, and differentiation ability of BMMNCs were detected. In vivo experiment, mice received 4 Gy total body irradiation (TBI), 3 mM spermidine were administered in the drinking water every day for 14 days prior to irradiation and then continued for 30 days after irradiation. Peripheral blood, bone marrow cell typing, level of reactive oxygen species (ROS), colony-forming ability of HSC, and transplantation-reconstitution capability were detected.

Results: In vitro experiments, spermidine significantly improved the survival rate of BMMNCs as well as the proliferation and differentiation ability of HSCs exposure to ionizing radiation (IR). In vivo, spermidine reduced levels of ROS in HSCs; spermidine attenuated long-term myeloid differentiation deviation induced by TBI. Spermidine promoted the proliferation and differentiation ability of stem cells, but failed to ameliorate the decreased engraftment capacity of bone marrow cells in mice exposed to TBI.

Conclusion: This study demonstrated that spermidine could promote the recovery of IR-induced inhibition of proliferation and differentiation ability of HSCs, partly through antioxidant effects. Whether combining spermidine with other radioprotectants could further increase protective efficacy and reduce the long-term bone marrow injury needs further investigation.

Keywords: Hematopoietic stem cells; Ionizing radiation; Reactive oxygen species; Spermidine.

MeSH terms

Animals
Antioxidants / pharmacology
Bone Marrow Cells
Hematopoietic Stem Cells
Mice
Mice, Inbred C57BL
Radiation Injuries*
Reactive Oxygen Species
Spermidine* / pharmacology
Whole-Body Irradiation

Substances

Reactive Oxygen Species
Spermidine
Antioxidants