Protection against cyclophosphamide-induced myelosuppression by ZPDC glycoprotein (24 kDa)

Immunomodulatory agents are often used to reduce myelosuppression and enhance immune response for cancer treatment. Cyclophosphamide (CTX) can induce oxidative stress in bone marrow resulting in suppression of anti-oxdiantive enzymes and causes myelosuppression. We isolated glycoprotein from Zanthoxylum piperitum DC fruit (ZPDC), and it consists of a carbohydrate (18%) and a protein (82%). The objective of this study was to investigate its protective activity against CTX-induced myelosuppression in Balb/c (n=6/group). The mice were orally administrated by ZPDC glycoprotein (10 and 20 mg/kg, BW) for 1 week in the presence or absence of CTX. Intracellular reactive oxygen species (ROS), anti-oxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)], cyclin kinase inhibitors (CKIs: p53, p21 and p27), cyclin D1/ cyclin dependent kinase (CDK) 4, PCNA and cytokines [interleukin (IL)-3, and granulocyte⁄ macrophage-colony-stimulating factor (GM-CSF)] were evaluated using biochemical activity, Western blot analysis, and ELISA. The results obtained from this study showed that CTX decreased spleen and thymic indices, bone marrow cellularity and expression of cyclin D1/CDK4 and PCNA, but it increased CKIs, whereas ZPDC glycoprotein (20 mg/kg, BW) resulted in vice versa in CTX-induced Balb/c. Expression of IL-3 and GM-CSF were normalized by ZPDC glycoprotein. Thus, this study suggested that ZPDC glycoprotein prevents oxidative stress and myelosuppression in CTX-induced mice and might be a potential immunomodulatory agent.