In vitro and in vivo evaluation of potential aluminum chelators.
The potential for aluminium (Al) chelation by different compounds was determined using 2 in vitro techniques. The formation of stable complexes with Al in an aqueous solution was evaluated using pulse polarography. This technique allowed the influence of temperature and calcium (Ca) to be studied for each compound. Certain compounds (EDDHA, HAES, citric acid and HBED) showed great chelation in the absence of Ca2+ at a temperature of 37 +/- 1 C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy allowed the efficiency of different substances to complex Al that were previously bound to serum proteins to be estimated. The kinetics of chelation and minimum efficient concentration have been determined for all products studied. EDDHA had chelation potential similar to DFO. The real efficacies of the compounds were studied in vivo to compare the effectiveness of repeated administrations of the best chelating agents (EDDHA, DFO, HAES and tartaric acid) on the distribution and excretion of Al after repeated i.p. administrations to rats. Intraperitoneal EDDHA significantly increased urinary metal (Al, Ca, Cu, Fe and Zn) excretion. These excretions may be correlated to a renal toxic potential property.
Graff
L
L
Laboratoire de Chimie Generale Appliquee a la Medecine, Faculte de Medecine, Universite Henri Poincare, Vandoeuvre les Nancy, France.
Muller
G
G
Burnel
D
D
D000535:Aluminum / Q000032:analysis* / Q000633:toxicity; D000818:Animals; D002104:Cadmium / Q000032:analysis; D002118:Calcium / Q000652:urine; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002951:Citrates / Q000008:administration & dosage / Q000494:pharmacology; D019343:Citric Acid; D003300:Copper / Q000032:analysis; D004492:Edetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D005029:Ethylenediamines / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007501:Iron / Q000032:analysis; D008297:Male; D011048:Polarography; D051381:Rats; D012995:Solubility; D013696:Temperature; D015032:Zinc / Q000032:analysis
D002614:Chelating Agents; D002951:Citrates; D005029:Ethylenediamines; D002104:Cadmium; C011813:ethylenediamine-N,N'-bis(2-hydroxyphenylacetic acid); D019343:Citric Acid; C037740:N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid; D003300:Copper; C007999:hydroxycitric acid; D004492:Edetic Acid; D000535:Aluminum; D007501:Iron; D015032:Zinc; D002118:Calcium