Removal of Fe3+ and Zn2+ from plasma metalloproteins by iron chelating therapeutics depicted with SEC-ICP-AES.
The iron chelation therapy drugs desferrioxamine B (DFO) and deferiprone (DFP) are used to treat iron overload patients, but not much is known about their adverse effects on other essential metals in vivo. After the addition of a clinically relevant dose of DFP or an equimolar dose of DFO to human plasma in vitro, the mixtures were analyzed by size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES). Simultaneous detection of the emission lines of copper, iron and zinc allowed the visualization of changes that these drugs exerted at the metalloprotein level. After the addition of DFP, a <10 kDa novel Fe-peak was detected and identified as (DFP)(3)Fe, whereas DFO resulted in the elution of a much smaller amount of Fe in this elution range. In fact, DFP was approximately 8-times more efficient than DFO regarding the removal of Fe from plasma proteins. The addition of both iron chelators also resulted in the elution of a <10 kDa novel Zn-peak. DFP abstracted twice as much Zn from plasma proteins compared to DFO. The identification of one of these peaks as (DFP)(2)Zn establishes a feasible biomolecular basis for the etiology of Zn-deficiency in patients that undergo long-term treatment with these drugs. Our results demonstrate that the analysis of plasma by SEC-ICP-AES can simultaneously provide insight into the efficacy of chelation therapy drugs and their adverse health effects at the metalloprotein level. Thus, SEC-ICP-AES emerges as a useful analytical tool to visualize health-relevant bioinorganic chemistry-related reactions of medicinal drugs in blood plasma in vitro.
Sooriyaarachchi
Melani
M
Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada.
Gailer
Jürgen
J
D001665:Binding Sites; D002850:Chromatography, Gel; D000077543:Deferiprone; D003676:Deferoxamine / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000737:chemistry* / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy; D008667:Metalloproteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011728:Pyridones / Q000737:chemistry / Q000627:therapeutic use; D012709:Serum Albumin / Q000737:chemistry; D013054:Spectrophotometry, Atomic; D015032:Zinc / Q000378:metabolism*
D007502:Iron Chelating Agents; D008667:Metalloproteins; D011728:Pyridones; D012709:Serum Albumin; D000077543:Deferiprone; D007501:Iron; D003676:Deferoxamine; D015032:Zinc