Treatment with Bone Marrow Products Acceler Ates Recovery from Chemotherapy Associated Leukopenia and Liver Injury in Tumour Bearing Mice (original) (raw)

2020

Abstract

Treatment with cyclophosphamide (CTX); a widely used anticancer drug, causes leukopenia which is the most critical associated side effect. The present work aimed to investigate the effects of treatment with bone marrow products on leukopenia and liver injury induced by CTX in Ehrlich ascetic carcinoma (EAC) mouse model. Adult female CD-1 mice were challenged with Ehrlich ascetic carcinoma (EAC) (2.5 x 105) cells on day 0 and then were inoculated 24 hours later with 100uL PBS or CTX (200 mg/kg) via intrapertioneal injection. The next day after CTX treatment, mice were treated for 5 consecutive days with granulocytes-colony stimulating factor (G-CSF; 250 µg/kg) and/or bone marrow lysate (100 µg/mouse) prepared from naive or CTX-treated mice via subcutaneous injection. Another groups of tumour-bearing mice were transferred with viable bone marrow cells (5 x 106) harvested from naive or CTX-treated mice. The results indicated that treatment with G-CSF induced recovery of the CTX-induced decreases in the numbers of bone marrow cells, splenocytes and peripheral blood leukocytes. While transfer of viable bone marrow cells resulted in recovery of bone marrow cell and spleen cell count only. Treatment of CTX-treated mice with bone marrow lysate prepared from naive or CTX-treated mice also induced recovery of the absolute number of lymphocytes. These effects were also associated with recovery from CTX-induced liver injury as observed by histopathological investigation. Of notes, treatment with bone marrow lysate prepared from naive or CTX-treated mice showed the highest recovery effects against CTX-induced lymphopenia. Finally, it is concluded that treatment with bone marrow products accelerates recovery of chemotherapy associated toxicity, opening a new avenue for further investigation to optimize their effects.

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