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Iron accumulation in HIV-infected patients

iron accumulation found in these patients is  caused by unknown mechanisms

Biometals. 2004 Aug;17(4):443-50.  Related Articles, Links  

Effects of AZT on cellular iron homeostasis.

Bozzi A, Brisdelli F, D’Alessandro AM, D’Andrea G, Lizzi AR, Rinaldi AC,
Oratore A.

Department of Biomedical Sciences and Technologies, University of L’Aquila, Via
Vetoio, Coppito 2, 67100 L’Aquila, Italy. bo…

3′-azido-3′-deoxythymidine (AZT), the first chemotherapeutic drug approved by
FDA for treatment of HIV-infected patients and still used in combination
therapy, has been shown to induce, upon prolonged exposure, severe bone marrow
toxicity manifested as anemia, neutropenia and siderosis. These toxic effects
are caused by inhibition of heme synthesis and, as a consequence, transferrin
receptor (TfR) number appears increased and so iron taken up by cells. Since
iron overload can promote the frequency and severity of many infections,
siderosis is viewed as a further burden for AIDS patients. We have previously
demonstrated that AZT-treated K562 cells showed an increase of the number of
TfRs located on the surface of the plasma membrane without affecting their
biosynthesis, but slowing down their endocytotic pathway. In spite of the
higher number of receptors on the plasma-membrane of AZT-treated cells,
intracellular accumulation of iron showed a similar level in control and in
drug-exposed cells. The chelating ability of AZT and of its phosphorylated
derivatives, both in an acellular system and in K562 cells, was also checked.
The results demonstrated that AZT and AZTMP were uneffective as iron chelators,
while AZTTP displayed a significant capacity to remove iron from transferrin
(Tf). Our results suggest that AZT may be not directly involved in the iron
overloading observed upon its prolonged use in AIDS therapy. The iron
accumulation found in these patients is instead caused by other unknown
mechanisms that need further studies to be clarified.

PMID: 15259365 [PubMed - in process]


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