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Radioprotection mediated by the haemopoietic stimulation conferred by AM5: a protein-associated polysaccharide
A Real1, G Güenechea, J A Bueren
1CIEMAT, Instituto de Medio Ambiente, Madrid, Spain.
Abstract:
The haemopoietic and radioprotective effects of a protein-associated polysaccharide named AM5, have been studied following i.v. injection in mice. A dose-related accumulation of the splenic granulocyte-macrophage colony-forming units (CFU-GM) and colony-forming units in the spleen (CFU-S) was observed in mice treated with doses ranging from 0.1 to 0.4 mg/kg of AM5. The accumulation of splenic CFU-S, CFU-GM and BFU-e (erythroid burst-forming units) was always maximal 5 days after treatment with 0.4 mg/kg of AM5, with increases over control values between 300% and 500%. When the number of haemopoietic progenitors was quantified in the bone marrow, only slight increases of CFU-S were obtained, corresponding to the administration of low doses of AM5 (0.1 mg/kg). However, significant increases of circulating CFU-S were observed following administration of higher doses of AM5, suggesting a mobilization of haemopoietic progenitors from this organ. A faster recovery of spleen CFU-GM was observed in mice treated with 0.4 mg/kg of AM5 3 days or 1 day prior to a sublethal irradiation, and at this later time AM5 produced a significant survival enhancement from 10% to 90% in mice irradiated with 7.6 Gy X-rays. This effect was correlated with an increase in the nadir of leucocytes, characteristic of the radiation syndrome.
Insights
The protein-associated polysaccharide AM5 enhances hematopoietic stem cell recovery and survival following irradiation in mice. AM5 treatment increased splenic colony-forming units and significantly improved survival rates after X-ray exposure.
Area of Science:
- Hematology
- Radiobiology
- Immunology
Background:
- Protein-associated polysaccharides are being investigated for therapeutic potential.
- Understanding hematopoietic and radioprotective effects is crucial for developing new treatments.
Purpose of the Study:
- To investigate the hematopoietic and radioprotective effects of AM5 in mice.
- To determine the dose-dependent effects of AM5 on hematopoietic progenitor cells.
- To evaluate AM5's efficacy in improving survival after irradiation.
Main Methods:
- Intravenous injection of AM5 in mice at varying doses (0.1-0.4 mg/kg).
- Quantification of splenic and bone marrow hematopoietic progenitors (CFU-GM, CFU-S, BFU-e).
- Assessment of survival rates and leukocyte nadir following sublethal irradiation.
Main Results:
- AM5 demonstrated dose-dependent increases in splenic CFU-GM, CFU-S, and BFU-e, peaking 5 days post-treatment.
- Higher AM5 doses led to increased circulating CFU-S, suggesting progenitor mobilization.
- AM5 treatment prior to irradiation accelerated spleen CFU-GM recovery and enhanced survival from 10% to 90%.
Conclusions:
- AM5 exhibits significant hematopoietic-stimulating and radioprotective properties.
- AM5 promotes the recovery of hematopoietic stem cells and enhances survival in irradiated mice.
- Further research into AM5 as a radioprotective agent is warranted.