Effective modulation of the haematopoietic toxicity associated with zidovudine exposure to murine and human haematopoietic progenitor stem cells in vitro with lithium chloride.
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, frequent thrombocytopenia, 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 haematopoietic progenitor stem cells following exposure to anticancer drugs and/or radiation in the treatment of malignant disease. We here report the results of studies designed to evaluate the effectiveness of lithium in reversing and/or protecting against either murine or human bone marrow derived haematopoietic progenitors, i.e. (CFU-GM, CFU-Meg, and BFU-E) when co-cultured in the presence of zidovudine in vitro. Lithium chloride (LiCl) reversed zidovudine toxicity to either murine or human derived CFU-GM and CFU-Meg that was optimal at a concentration of 1 mM (P less than 0.05). However, the addition of lithium failed to influence zidovudine toxicity toward either murine or human BFU-E. In summary, these results support the scant clinical studies that have described the presence of neutrophilia and/or thrombopoiesis in zidovudine-treated AIDS patients receiving lithium. In addition, these data further confirm the need for more detailed evaluation of lithium as an adjuvant agent to reduce the haematopoietic toxicity associated with the use of antiviral therapy in HIV-infected patients.
Gallicchio
V S
VS
Department of Medicine, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, Lexington.
Hughes
N K
NK
D000818:Animals; D002712:Chlorides / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D015215:Zidovudine / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D002712:Chlorides; D015215:Zidovudine; D008094:Lithium; D018021:Lithium Chloride