Abstract

Background: Several studies documented the non-hematologic clinical therapeutic uses of recombinant human erythropoietin (EPO). On the other hand, hypertension, thromboembolism, and increased oxidative stress were toxic effects related to the increased hematocrit (Hct) with recombinant human EPO treatment. Accordingly, alternate strategies to reduce erythropoietic activity and other potential side effects of EPO will greatly improve its non-hematopoietic clinical applicability. Aims and Objectives: Our objective was to demonstrate whether curcumin treatment could attenuate the effect of recombinant human EPO on erythropoiesis in EPO-induced polycythemia, and if so, whether this effect is mediated by changing concentrations of iron and its key regulator hormone hepcidin in rats.
Materials and Methods: Totally 24 male albino Sprague-Dawley rats were included in this study. Rats were equally divided into four groups: Control group, curcumin-treated group, EPO-induced polycythemia group, and curcumin + EPO-induced polycythemia group. Blood indices and serum concentrations of iron, ferritin, and hepcidin were measured.
Results: EPO treatment caused significant increase in hemoglobin (Hb), red blood cells, and Hct versus other study groups (P < 0.05). Curcumin treatment significantly decreased Hct in curcumin-treated group versus control and EPO-induced polycythemia groups (P = 0.021 and 0.008, respectively). Serum iron concentrations were significantly decreased in curcumin + EPO-induced polycythemia group versus control group. Serum ferritin concentrations were significantly decreased in all treated groups versus the control group. Serum hepcidin concentrations were significantly decreased in EPO-induced polycythemia group and curcumin + EPO-induced polycythemia group versus control group. Conclusion: The presented data suggest a potentially attenuating effect of curcumin administration on recombinant human EPO-induced polycythemia. This effect may be mediated by promoting iron deficiency. However, further studies are required to address the safety of this combination treatment and interspecies differences in iron metabolism between rats and human in addition to have better understanding of the role of the hepcidin.