Concomitant treatment with beta-glucan and G-CSF ameliorates altered biochemical indices after cyclophosphamide-induced leukopenia in mice

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Cyclophosphamide (CTX) is a DNA-alkylating chemotherapeutic agent and leads to leucopenia and hepatocyte injury. Granulocyte colony-stimulating factor (G-CSF) promotes granulocyte counts and increases leukocytes count. Beta (β)-glucans affect bone marrow cellularity and stem cell mobilization. This study aimed to investigate the effect of β-glucan in combination with G-CSF on leucopenia and hepatocytes injury induced by CTX in mice. Animals were injected with CTX, G-CSF and/or β-glucan for five days, then leukocyte counts and biochemical assays were performed. Our results showed that CTX administration decreased splenocytes and total white blood cells counts. Furthermore, CTX administration led to hepatocyte oxidative stress which was characterized by increased pro-oxidants (thiobarbituric acid reactive substances and xanthine oxidase) and decreased anti-oxidant levels (glutathione peroxidase) and energy disturbance and cell mobilization arrest due to the partial inhibition of adenosine triphosphatase and mannosidase. As a result, hepatocyte injury was observed as indicated by serum aspartate aminotransferase and alanine aminotransferase elevation. β-glucan alone or combined with G-CSF successfully normalized the biochemical parameters and the alteration in cell counts arising from CTX administration. In conclusion, CTX causes leukopenia and liver necrosis through the stimulation of oxidative stress, which leads to inflammation. Both G-CSF and glucan counteract this action through their anti-oxidant and anti-inflammatory properties.