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

•Spermidine showed protective effect against radiation-induced bone marrow cell damage in vitro.•Spermidine inhibits total body irradiation (TBI)-induced excess chronic oxidative stress in HSCs in vivo.•Spermidine recovered the reduction of the phenotype and counts of bone marrow cells in the irradiated mice.•Spermidine had a protective effect on radiation-induced impaired ability of proliferation and differentiation of HPC and HSC.•Competitive repopulation assay implied that spermidine had no protective effect on the damage of HSC induced by irradiation. 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. 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. 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. 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 fu