Norcantharidin alleviates cyclophosphamide-induced immunosuppression and leukopenia in mice through NF Kappa B pathway

Purpose: To investigate the effect of norcantharidin (NCTD) on cyclophosphamide (CY)-induced immunosuppression and leukopenia in mice.Methods: Cyclophosphamide (80 mg/kg/day) was intraperitoneally administered to mice from day 1 to 3 and day 9, and from day 4 to 10, NCTD (1, 2 and 4 mg/kg) was intraperitoneally administered. The counts of white blood cells (WBC), red blood cells (RBC) and platelets (PLT) in peripheral blood were determined, followed by the evaluation of mouse spleen and thymus indices. Histopathological examination was performed using hematoxylin-eosin (H & E) staining. In addition, the serum levels of immunoglobulins and cytokines were determined using enzyme-linked immunosorbent assay (ELISA), while plenetic T lymphocyte subsets were assessed by flow cytometry. The expression levels of p65, p -p65, IKB alpha, and p-IKB alpha in spleen tissues were determined by immunoblotting.Results: Administration of NCTD (1, 2 and 4 mg/kg) increased blood cell counts, and alleviated injuries on splenocytes and thymocytes in CY-treated mice, accompanied by decline in spleen and thymus indices. NCTD ameliorated CY-induced immunosuppression by inhibiting the cytokines but increased the immunoglobulins. CD4+ and CD8+ T lymphocyte expressions were enhanced, especially at the high dose of NCTD (4 mg/kg). Besides, NCTD at high doses (2 and 4 mg/kg) significantly activated NF-KB pathway.Conclusion: Administration of NCTD alleviates CY-induced leukopenia and immunosuppression in mice through activation of NF-KB pathway, thus providing a lead for the potential treatment of chemotherapy-induced leukopenia and immunosuppression.