Erythropoietin-Like Effects of Dihydroartemisinin in Wistar Albino Rats

Abstract

Artemisinin drugs were active during the intra-ery throcytic stage of malaria parasite infection. The activity of artemisinin and syntheti c endoperoxides was related to their interaction wi th heme. The electrophillic intermediate formed from a rtemisinin 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 rat s. Approach: The dosages of DHA tested on 5 test adult Wistar albino rats (weight = 106-140 grams) w ere 1, 2, 60 or 80 mg Kg -1 rat weight of DHA by oral intubation for 5 or 7 days. Four rats of simil ar weight which served as controls in each experime nt were given distilled water equivalents of the admin istered 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 a fter which the treatment was repeated. Results: The findings of the study showed that Dihydroartemisini n (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 contro ls. 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 in hibited 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 comp osition of the blood cell types like the presence o f large numbers of reticlocytes and left-shifted neut rophils in the blood samples of 5-day DHA -treated rats but not in those of 7-day DHA treated rats ind icated 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 i nhibition of haemopoesis by a negative feed-back effect on haemopoiesis suggest that DHA has erythropoietin-like properties.