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Reduction of Sb(V) in a Human Macrophage Cell Line Measured by HPLC-ICP-MS

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Abstract

Drugs based on pentavalent antimony are first-line treatment of the parasite disease leishmaniasis. It is generally believed that Sb(V) acts as a prodrug, which is activated by reduction to Sb(III); however, the site of reduction is not known. It has been hypothesised that the reduction takes place in the parasites’ host cells, the macrophages. In this study, the human macrophage cell line Mono Mac 6 was exposed to Sb(V) in form of the drug sodium stibogluconate (Pentostam™). Cell extracts were analysed for Sb species by high-performance liquid chromatography with inductively coupled plasma-mass spectrometry detection. We found that Sb(V) is actually reduced to Sb(III) in the macrophages; up to 23% of the intracellular Sb was found as Sb(III). Transfer of the cells to Sb-free medium rapidly decreased their Sb(V) and Sb(III) content. Induction of the cell’s production of reactive oxygen species did not have any marked effect on the intracellular amounts of Sb(III).

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Author notes

  1. Helle Rüsz Hansen

    Present address: Department of Chemistry, University of Aberdeen, Meston Walk, Aberdeen, AB24 3UE, Scotland, UK

Authors and Affiliations

  1. Department of Pharmaceutics and Analytical Chemistry, University of Copenhagen, Universitetsparken 2, DK, 2100, Copenhagen Ø, Denmark

    Claus Hansen, Helle Rüsz Hansen, Bente Gammelgaard & Stefan Stürup

  2. Department of Pharmacology and Pharmacotherapy, University of Copenhagen, Universitetsparken 2, DK, 2100, Copenhagen Ø, Denmark

    Erik Wind Hansen

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  1. Claus Hansen
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  2. Erik Wind Hansen
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Correspondence to Claus Hansen.

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Hansen, C., Hansen, E.W., Hansen, H.R. et al. Reduction of Sb(V) in a Human Macrophage Cell Line Measured by HPLC-ICP-MS. Biol Trace Elem Res 144, 234–243 (2011). https://doi.org/10.1007/s12011-011-9079-9

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  • DOI: https://doi.org/10.1007/s12011-011-9079-9

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