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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Gamma Rays / adverse effects
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Hematopoietic Stem Cells / radiation effects
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Hydroxamic Acids / metabolism
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Hydroxamic Acids / pharmacology*
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Indoles / metabolism
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Indoles / pharmacology*
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Male
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Matrix Metalloproteinase Inhibitors / pharmacology
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Mice
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Mice, Inbred C57BL
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Oxidative Stress / radiation effects
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Radiation Injuries / drug therapy*
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Reactive Oxygen Species / pharmacology
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Spleen / radiation effects
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Transforming Growth Factor beta1 / radiation effects
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Tumor Necrosis Factor-alpha / radiation effects
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Whole-Body Irradiation / adverse effects*
Substances
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Hydroxamic Acids
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Indoles
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Matrix Metalloproteinase Inhibitors
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Reactive Oxygen Species
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Transforming Growth Factor beta1
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Tumor Necrosis Factor-alpha
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ilomastat
Grants and funding
BZ, XL(second) and DQ were supported by the Military Medical Scientific and Technological Project [AWS17J009, BWS16J007, 2018ZX09J18102], BH was supported by the National Natural Science Foundation of China [11635013]. Baoquan Zhao took charge of the experimental design, data analysis and manuscript revise. Xiaoman Li performed experiments, analyzed the results and wrote the manuscript. Xingzhou Li, Dongqin Quan and Fang Zhang helped with experiments, data interpretation and manuscript preparation. Burong Hu helped with the experimental design, data analysis and manuscript revise. All authors read and approved the final manuscript.