Evidences that zidovudine (AZT) could not be directly responsible for iron overload 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 currently used in combination therapy of human immunodeficency virus (HIV) infection. 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 and iron overload have been in evidence over the last few years. In this report, we have examined some features of zidovudine 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 and some of its phosphorylated derivatives in solution. The iron chelating ability of AZT toward the intracellular 'chelatable' iron pool was also evaluated. Finally, we investigated the effect of AZT on both iron and transferrin uptake. Our findings indicate that AZT per se cannot be directly responsible for the development of the iron overload found in human or animal models, for which other possible mechanisms are claimed to be involved.
D'Alessandro
A M
AM
Department of Biomedical Sciences and Technology, University of L'Aquila, I-67100, L'Aquila, Italy.
Rinaldi
A C
AC
D'Andrea
G
G
Brisdelli
F
F
Di Ciccio
L
L
Di Giulio
A
A
Oratore
A
A
Bozzi
A
A
D019380:Anti-HIV Agents / Q000009:adverse effects*; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000139:chemically induced*; D020014:K562 Cells; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*; D015215:Zidovudine / Q000009:adverse effects*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D007501:Iron