Renal excretion of aluminium in the rat: effect of citrate infusion.
When aluminium is administered intravenously to rats, the speciation of the aluminium has a major effect on its renal excretion. Aluminium administered as citrate is much more effectively excreted than that administered as chloride or sulphate. This suggests that citrate could be therapeutically useful in patients who have been exposed to aluminium. Accordingly, we have performed two series of experiments in rats, in which a citrate infusion (intravenous), was begun either immediately after, or one hour after, the administration of an intravenous aluminium sulphate bolus. Both protocols led to markedly enhanced aluminium excretion compared to controls in which only 0.7% NaCl was infused. The enhancement of aluminium excretion was 783% if citrate infusion was begun immediately after aluminium administration, and 335% if the citrate infusion began after an hour delay. The increased excretion was due to an increase in the freely filterable fraction of aluminium. In the control experiments, in which aluminium sulphate administration was followed by 0.7% NaCl infusion, aluminium was found to be deposited in the liver. Administration of citrate one hour after the aluminium bolus did not reduce this liver deposition. The results indicate that a fraction of the plasma aluminium is accessible to the citrate infused and can thereby be converted into a filterable form which can be excreted. It appears that, for maximum therapeutic effect, citrate should be infused as rapidly as possible after an aluminium load, to limit aluminium binding to ligands which allow it to enter cells.
Lote
C J
CJ
Department of Physiology, University of Birmingham, UK.
Willmott
K
K
Wood
J A
JA
Thewles
A
A
Freeman
M
M
D000534:Alum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000535:Aluminum / Q000097:blood / Q000652:urine*; D000818:Animals; D001665:Binding Sites; D002951:Citrates / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D004195:Disease Models, Animal; D007262:Infusions, Intravenous; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000008:administration & dosage / Q000633:toxicity
D000534:Alum Compounds; D002951:Citrates; C041524:aluminum sulfate; D012965:Sodium Chloride; D000535:Aluminum