Aluminum speciation studies in biological fluids. Part 5. A quantitative investigation of A1(III) complex equilibria with desferrioxamine, 2,3-dihydroxybenzoic acid, Tiron, CP20 (L1), and CP94 under physiological conditions, and computer-aided assessment of the aluminum-mobilizing capacities of these ligands in vivo.
While the involvement of environmental aluminum toxicity in the advent of senile dementias is still debated, acute aluminum toxicity of iatrogenic origin is well documented. So far, the only treatment available against it has been desferrioxamine (DFO), which induces major side effects. New drugs are thus highly desirable, and possible DFO substitutes have already been considered through various techniques. An important test for such new drugs is to assess their A1-mobilizing capacity in vivo. This can be done by computer-aided speciation provided formation constants for the corresponding A1(III) complexes are known beforehand. The present work reports an investigation of A1(III) complex equilibria with five sequestering ligands including DFO, and predicts the respective capacities of these to mobilize aluminum in vivo under normal and inflammatory conditions.
ICMPS-CNRS FR1744, Université Paul Sabatier, Toulouse, France.
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Desroches
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Biron
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Berthon
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000378:metabolism*; D000535:Aluminum / Q000378:metabolism*; D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D002614:Chelating Agents / Q000009:adverse effects / Q000378:metabolism*; D003198:Computer Simulation; D000077543:Deferiprone; D003676:Deferoxamine / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D062385:Hydroxybenzoates / Q000378:metabolism; D007202:Indicators and Reagents; D007249:Inflammation / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism*; D008024:Ligands; D011728:Pyridones / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D015203:Reproducibility of Results
D002614:Chelating Agents; D062385:Hydroxybenzoates; D007202:Indicators and Reagents; D007502:Iron Chelating Agents; D008024:Ligands; D011728:Pyridones; C068543:1,2-diethyl-3-hydroxypyridin-4-one; D000077543:Deferiprone; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; C009135:2,3-dihydroxybenzoic acid; D000535:Aluminum; D003676:Deferoxamine