게잡이 원숭이에 있어 rHuEPO의 4주간 투여 후 혈액학 및 조직병리학적 변화

초록

We investigated effects of recombinant human erythropoietin (rHuEPO) on body weight, organ weight, hematology, serum biochemistry, and histopathology in 6 male cynomolgus monkeys (Macaca fascicularis). Six monkeys, composed of treatment and control groups, were intravenously administered 3 times per week at doses of 0 and 2730 IU/ 0.1 ml/kg with rHuEPO for 4 weeks. rHuEPO treatment did not show any change in body weights for 4 weeks and caused an increase of organ weight in spleen, salivary gland, kidney, and liver. rHuEPO treatment increased significantly mean corpuscular hemoglobin concentration, reticulocyte, and red cell distribution width from day 3 of the study and red blood cells, hemoglobin, and hematocrit levels were increased significantly from day 7 or 10 up to day 28. For an increase in red cell distribution width, it was found to a large extent on day 7, day 10, and day 14, while was found to a small extent on day 21 and day 28. It increased platelet distribution width on day 10, day 14, day 21, and day 28. Histopathological examination showed that rHuEPO treatment caused an extramedullary hemopoiesis in spleen and bone marrow hyperplasia in sternum and femur. The results indicated that rHuEPO treatment caused an increase in platelet- and RBC-related parameters, extramedullary hemopoiesis of spleen, and bone marrow hyperplasia of sternum and femur. The present study will be valuable in the proper interpretation and validation of general toxicology studies for biogeneric drugs including rHuEPO in cynomolgus monkeys.

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