Erythropoietin-Like Effects of Dihydroartemisinin in Wistar Albino Rats

Abstract

Artemisinin drugs were active during the intra-erythrocytic stage of malaria parasite infection. The activity of artemisinin and synthetic endoperoxides was related to their interaction with heme. The electrophillic intermediate formed from artemisinin in the presence of heme alkylates the protein portion of hemoglobin preferentially to the heme portion. Problem statement: Since there might be an interaction between artemisinin and the heme of the blood, we studied the effects of 5-day and 7-day oral Dihydroartemisinin (DHA) treatments with 5 dosage regimens of dihydroartemisinin on the blood and six vital organs of Wistar albino rats. Approach: The dosages of DHA tested on 5 test adult Wistar albino rats (weight = 106-140 grams) were 1, 2, 60 or 80 mg Kg^-1 rat weight of DHA by oral intubation for 5 or 7 days. Four rats of similar weight which served as controls in each experiment were given distilled water equivalents of the administered doses of DHA. Another group of 5 test rats and four control rats (weight 75-90 gms) were given 1 mg kg^-1 rat weight of DHA or distilled water for 5 or 7 days and were allowed to rest for one week after which the treatment was repeated. Results: The findings of the study showed that Dihydroartemisinin (DHA) had erythropoietin-like properties. In the study DHA produced dose, repetition and time dependent statistically significant increases in the Packed Cell Volume (PCV) (P<0.01-0.03) and the total White Blood Cell count (WBC) (P<0.01) of the DHA-treated rats which was absent in the controls. The 7-day DHA treatments produced lower statistically significant increases of the PCV (P<0.01-03) and the WBC (P<0.01) than the 5-day DHA treatments. Conclusion: This result suggested that the administered DHA inhibited its own stimulated statistically significant increases in the PCV and the WBC of the treated rats through an inhibitory (negative) feed-back effect. The structure and composition of the blood cell types like the presence of large numbers of reticlocytes and left-shifted neutrophils in the blood samples of 5-day DHA -treated rats but not in those of 7-day DHA treated rats indicated that new haemopoiesis was actively going on in the first 5 days of DHA treatment but had slowed down by the sixth and seventh day of treatment. The initial stimulation of haemopoiesis and later inhibition of haemopoesis by a negative feed-back effect on haemopoiesis suggest that DHA has erythropoietin-like properties.