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Year:
1998
| Volume: 6
| Issue: 4
| Pages: 151-154
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Original Article |
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THE EFFECT OF PEGYLATED RECOMBINANT HUMAN MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR (PEG-RHUMGDF) ON THE CYCLOPHOSPHAMIDE INDUCED THROMBOCYTOPENIA IN MICE
Radoslav BOROTA, Jela BOROTA |
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DOI:
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Abstract: |
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Background: The major adverse effect of most cancer chemotherapy is myelosuppression with resultant neutropenia and thrombocytopenia that remains the major dose limiting factors for high-dose chemotherapy. Theoretically, one of the ways to overcome this problem was the presumption that hematopoietic growth factors could maintain the hematopoiesis in the presence of so high doses of cytostatics which might kill almost all the malignant cells. This presumption was first proved for granulocytopoiesis but it could not be applied for thrombocytopoiesis until now because only recently there became available a thrombopoietin preparation - pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), in sufficient amounts for clinical use.
Materials and Methods: Groups of mice were submitted to platelet count estimation, and 24 hours later, on the day 0, injected with active substances, intravenously, subcutaneously or intraperitoneally, as it is depicted on the graphs. After 1 to 8 days blood samples were taken and the platelet count estimated again. Three experiments were completed: first by intraperitoneal injections of several doses (4-12 mg per mouse 160-480 mg/kg) of cyclophosphamide (Cy), second by intravenous or subcutaneous injections of 20mg/kg PEG-rHuMGDF, and the third by intraperitoneal injection of 4 mg of Cy (160mg/kg) followed by subcutaneous injection of 20mg/kg PEG-rHuMGDF.
Results: A single dose of Cy in several amounts caused a dose dependent decrease of the platelet count with a nadir on fourth or fifth day after application and an increase to the starting values after eight or ten days. A single dose of PEG-rHuMGDF produced a dramatic rise of the platelet count with its maximum on the sixth day.. The comparison between the platelet count in peripheral blood of animals receiving only Cy and those which were injected additionally with PEG-rHuMGDF showed a constant and significant difference, because the platelet count decrease is significantly smaller in mice treated additionally with PEG-rHuMGDF, especially on days 4, 6 and 7.
Conclusion: Administration of PEG-rHuMGDF in the presented murine experimental model can significantly improve the thrombocytopenia caused by Cyclophosphamide. This suggests that it can also be very helpful in treating myelosuppression at patients receiving cytostatic therapy which includes this cytostatic drug. |
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Key words:
THROMBOPOIETIN; THROMBOCYTOPENIA; CYCLOPHOSPHAMIDE |
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