Gallicchio V S, Hughes N K, Tse K F
Haematology/Oncology Division, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, Lexington.
J Intern Med. 1993 Mar;233(3):259-68. doi: 10.1111/j.1365-2796.1993.tb00985.x.
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.
药物齐多夫定（AZT）是一种合成的胸腺嘧啶类似物，已用于治疗获得性免疫缺陷综合征（艾滋病）。齐多夫定的临床使用已引发造血毒性，表现为贫血、中性粒细胞减少和整体骨髓抑制。单价阳离子锂已被证明是一种有效药物，能够调节造血的多个方面，如诱导中性粒细胞增多、血小板生成，以及在暴露于治疗恶性疾病常用剂量的抗癌药物和/或辐射后保护造血祖干细胞免受抑制。我们在此报告旨在评估锂在剂量递增的齐多夫定存在下对正常小鼠进行体内给药时逆转齐多夫定诱导的造血抑制有效性的研究结果。碳酸锂（Li2CO3）通过外周白细胞、血小板以及CFU-GM和CFU-Meg造血祖细胞数量的增加来衡量，可逆转齐多夫定毒性；然而，锂在体内逆转与齐多夫定使用相关的红细胞生成减少方面效果不佳。这些结果进一步证实了锂可有效逆转与抗病毒药物齐多夫定相关的骨髓抑制和血小板减少的发展，但在改善贫血诱导方面效果较差。
