Abstract
Ilomastat, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), has drawn attentions for its function in alleviating radiation damage. However, the detailed mechanisms of Ilomastat’s protection from animal model remain not fully clear. In this study, the C57BL/6 mice were pre-administrated with Ilomastat or vihicle for 2 h, and then total body of mice were exposed to 6 Gy of γ-rays. The protective effect of Ilomastat on the hematopoietic system in the irradiated mice were investigated. We found that pretreatment with Ilomastat significantly reduced the level of TGF-β1 and TNF-α, and elevated the number of bone marrow (BM) mononuclear cells in the irradiated mice. Ilomastat pretreatment also increased the fraction of BM hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) at day 30 after irradiation, and protected the spleen of mouse from irradiation. These results suggest that Ilomastat promotes the recovery of hematopoietic injury in the irradiated mice, and thus contributes to the survival of mouse after irradiation.
Highlights
Our previous studies showed that Ilomastat, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), could improve the survival of mice after γ-ray irradiation [1]
These results demonstrate that Ilomastat pretreatment could significantly reduce the levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1), and increase the levels of hematopoietic growth factor in serum of the irradiated mice
We determined the number of Bone marrow nucleated cells (BMNC) at day 10 and 20 post-total body irradiation (TBI), and both the BMNC count decreased in the irradiated mice only
Summary
Our previous studies showed that Ilomastat, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), could improve the survival of mice after γ-ray irradiation [1]. High-dose ionizing irradiation (IR) can result in severe acute radiation syndrome (ARS) [2,3,4]. Depletion of peripheral blood cells and immunosuppression are the main characters of ARS [5,6]. A number of compounds have been reported to reduce radiationinduced hematopoietic injury and improve the survival of the irradiated mice [5,7]. The extracellular matrix (ECM), a major component of hematopoietic microenvironment, which alternates in the structure and/or function may contribute to the development of hematologic disorders [8,9,10].
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