[Deferoxamine promotes recovery of bone marrow hematopoietic function in mice exposed to a sublethal dose of X-ray irradiation].

OBJECTIVE

To evaluate the effect of deferoxamine (DFO) on bone marrow hematopoietic function in C57 mice exposed to a sublethal dose of X-ray irradiation.

METHODS

C57 mice exposed to a sublethal dose (5.4 Gy, 1.0 Gy/min) of total body X-ray irradiation (TBI) were treated with subcutaneous injection of 100 mg/kg DFO, with normal saline as the control, on a daily basis for 10 and 20 consecutive days. Body weight changes of the mice were monitored every 3 days. Five mice were selected from each group at 10 and 20 days for examination of blood cell counts, bone marrow nucleated cell counts, percentage of bone marrow CD34 cells, bone marrow pathology, and expressions of cleaved PARP-1, cleaved caspase-3, VEGF, GPX4, and SLC7A11 in the nucleated cells.

RESULTS

The body weight of the mice decreased significantly on day 3 in TBI and DFO groups (<0.05), and to the lowest on day 6 in TBI group (<0.01). Blood cell counts and bone marrow nucleated cell counts of the mice were significantly decreased at 10 and 20 days following TBI (<0.01). On day 10 following TBI, the mice showed significantly decreased nucleated cells and the presence of adipocytes in the bone marrow, where increased expressions of cleaved PARP-1 and cleaved caspase-3 and lowered expressions of GPX4 and SLC7A11 were detected in the nucleated cells (<0.05). In the mice exposed to TBI, treatment with DFO significantly increased CD34 cell percentage (<0.001), decreased the expressions of cleaved PARP-1 and cleaved caspase-3, and increased the expressions of GPX4, SLC7A11 and VEGF in the bone marrow nucleated cells (<0.05). DFO treatment significantly increased blood cell counts and bone marrow nucleated cells in mice at 20 days following TBI (<0.05).

CONCLUSION

DFO improves bone marrow hematopoiesis in mice with sublethal-dose TBI by inhibiting apoptosis and ferroptosis of bone marrow nucleated cells and promoting VEGF expression and CD34 cell proliferation.