ArticleInternational journal of radiation biology2025
Imidazolyl ethanamide pentandioic acid promotes hematopoietic recovery following sublethal radiation in a murine model.
Article in International journal of radiation biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeHematopoietic acute radiation syndrome (H-ARS) results from bone marrow (BM) damage, leading to depletion of myeloid and lymphoid cells and increasing infection, hemorrhage, and mortality risks. Imidazolyl ethanamide pentandioic acid (IEPA), an orally bioavailable molecule, alleviates chemotherapy-induced myelosuppression and may similarly mitigate H-ARS. This study examines whether IEPA, alone or with granulocyte-monocyte colony-stimulating factor (GM-CSF), promotes recovery of hematopoietic stem and progenitor cells (HSCs/HPCs) after sublethal total body irradiation (TBI). MATERIALS AND
methodsMice received 5 Gy TBI followed by vehicle, IEPA (days 1-3), GM-CSF (days 1-5), or IEPA+GM-CSF. Recovery was assessed by body weight, blood counts, flow cytometry, clonogenic assays, BM megakaryocytes, and splenic CD34
resultsIEPA increased body weight 2.5-fold by day 7, while IEPA+GM-CSF showed 2.5-fold and 3.3-fold increases on days 7 and 21, respectively. IEPA promoted recovery of HSCs/HPCs, multipotent progenitors (MPP2), myeloid and lymphoid progenitors, BM megakaryocytes, and splenic CD34+ cells. IEPA+GM-CSF improved in vitro self-renewal but offered no major in vivo advantage over IEPA alone, except for a 159-fold recovery in erythroid progenitors. All treatments reduced γ-H2AX expression in Lin- and HPCs on day 21, indicating less DNA damage.
conclusionsOur results reveal that IEPA attenuated radiation-induced DNA damage and improved recovery of HSCs/HPCs, myeloid as well as lymphoid progenitors, accompanied by increases in platelets in blood, megakaryocytes in BM and splenic CD34
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