Luteolin mitigates radiation-induced hematopoietic and immune system long-term damage in mice

Ionizing radiation (IR) can induce long-term alterations in the hematopoietic and immune systems. This study aimed to investigate the potential of luteolin (with known anti-inflammatory and anti-senescence properties), a natural flavonoid, to mitigate radiation-induced hematopoietic and immune system long-term damage in a mouse model. C57BL/6 mice were subjected to single whole-body irradiation (WBI) to establish a model of radiation-induced long-term damage, with five mice per group. WBI was performed using a γ-ray irradiator at a dose rate of 0.88 Gy/min, with a total radiation dose of 6 Gy. Four months post-IR, mice were administered luteolin (0.5 mg/kg/day) via oral gavage for two months. Flow cytometry was employed to analyze peripheral blood counts, bone marrow hematopoietic stem/progenitor cells (HSPCs) populations, and immune cell compositions in the thymus, spleen, and mesenteric lymph nodes (MLNs). Senescence-associated β-galactosidase (SA-β-Gal) staining and immunohistochemical analysis of p16 and p21 proteins were performed to assess aging-related changes in the spleen and thymus. WBI significantly reduced white blood cell (WBC) counts and induced myeloid–lymphoid skewing, with increased neutrophils and decreased lymphocytes, while also reducing red blood cell (RBC) counts and hemoglobin (HGB) levels. Luteolin did not alter total WBC counts but partially restored lymphocyte proportions and improved RBC and HGB levels. In bone marrow, WBI disrupted the HSPC compartment, decreasing LSKs and CD34+ LSKs while expanding CD34− LSKs and MEPs; these changes were partially reversed by luteolin. In immune organs, luteolin alleviated radiation-induced senescence in the thymus and spleen, increased B-cell proportions, and reduced macrophage accumulation, with minimal effects on T-cell subsets. Luteolin partially mitigates radiation-induced long-term injury by attenuating cellular senescence and modulating hematopoietic and immune system alterations. These results suggest that luteolin may represent a potential adjunctive strategy for alleviating long-term hematopoietic and immune damage following radiation exposure.