Modulation of the haematopoietic toxicity associated with zidovudine in vivo with lithium carbonate.

Abstract

The drug zidovudine (AZT), a synthetic thymidine analogue, has been used in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical use of zidovudine has induced haematopoietic toxicity manifested by anaemia, neutropenia, and overall bone marrow suppression. The monovalent cation lithium has been shown to be an effective agent capable of modulating several aspects of haematopoiesis such as the induction of neutrophilia, thrombopoiesis, and protection against suppression of hematopoietic progenitor stem cells following exposure to anti-cancer drugs and/or radiation at doses commonly used in the treatment of malignant disease. We report here the result of studies designed to evaluate the effectiveness of lithium in reversing zidovudine-induced haematopoietic suppression when administered to normal mice in vivo in the presence of dose-escalation zidovudine. Lithium carbonate (Li2CO3) reversed zidovudine toxicity as measured by increases in peripheral WBC, platelets, and CFU-GM and CFU-Meg haematopoietic progenitors; however lithium was insufficient in reversing the reduction of erythropoiesis associated with zidovudine use in vivo. These results further confirm the effective use of lithium to reverse the development of myelosuppression and thrombocytopenia associated with the anti-viral drug zidovudine, but is less effective in ameliorating the induction of anaemia.