Binding of aluminium to plasma proteins: comparative effect of desferrioxamine and deferiprone (L1).
Ultramicrofiltration techniques were used to study both the binding of aluminium to high molecular weight proteins in the presence of different concentrations of desferrioxamine and deferiprone (L1) and the kinetics of aluminium release from human serum proteins. Human serum from healthy volunteers was used in all studies. The serum was spiked with aluminium (100 micrograms/l) and different concentrations of chelators. Ultramicrofiltration was performed with Amicon YMT membranes which had a nominal cut-off of 30,000 Da. Aluminium was measured by graphite furnace atomic absorption spectrometry in total serum and ultrafiltered fluid. Deferiprone shows a higher capability to displace aluminium from serum proteins (80%) than desferrioxamine (60%) at equivalent concentrations of the chelators. The kinetics of the release were also faster for deferiprone, taking 20 min to achieve its maximum effect, whereas, desferrioxamine achieved only 80% of its maximum effect after 2 h. Thus, deferiprone could be an attractive alternative to desferrioxamine, as an aluminium chelator agent.
Unidad de Investigación, Metabolismo Oseo y Mineral, Hospital General de Asturias, Oviedo, Spain.
J L
JL
Fernández-Martín
P
P
Menéndez-Fraga
M A
MA
Canteros
J B
JB
Díaz-López
J B
JB
Cannata-Andía
D000535:Aluminum / Q000097:blood*; D001798:Blood Proteins / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D000077543:Deferiprone; D003676:Deferoxamine / Q000494:pharmacology*; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D007700:Kinetics; D011485:Protein Binding; D011728:Pyridones / Q000494:pharmacology*; D012016:Reference Values; D013054:Spectrophotometry, Atomic / Q000379:methods; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors; D014462:Ultrafiltration / Q000379:methods
D001798:Blood Proteins; D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D000535:Aluminum; D003676:Deferoxamine