Evidences that zidovudine (AZT) could not be directly responsible for ironoverload in AZT-treated patients: an in vitro study

Zidovudine (3'-azido-3'-deoxythymidine or azidothymidine, AZT) has been the first antiretroviral agent approved for clinical use, and it is still curr ently used in combination therapy of human immunodeficency virus (HIV) infe ction. On the basis of increasing clinical reports and in vitro studies, a strict correlation between AZT treatment of HIV positive patients and both the development of anemia acid iron overload have been in evidence over the last few years. In this report, we have examined some features of zidovudi ne to better assess a likely implication of this drug in iron overload. For this purpose, we first determinated the iron chelating ability of both AZT arid some of its phosphorylated derivatives in solution. The iron chelatin g ability of AZT toward the intracellular 'chelatable' iron pool was also e valuated. Finally, we investigated the effect of AZT on both iron and trans ferrin uptake. Our findings indicate that AZT per se cannot be directly res ponsible for the development of the iron overload found in human or animal models, for which other possible mechanisms are claimed to be involved. (C) 2000 Elsevier Science B.V. All rights reserved.