Renal filtration and excretion of aluminium in the rat: dose-response relationships and effects of aluminium speciation.
The known toxicity of aluminium, and the toxicity of agents (such as desferrioxamine) used to remove aluminium from the body, has prompted us to investigate whether there may be ways of enhancing aluminium excretion by exploiting the normal renal handling of aluminium. Aluminium (as sulphate or citrate) was administered intravenously to conscious rats at doses ranging from 25 micrograms (0.93 mumol) to 800 micrograms (29.6 mumol) aluminium, and aluminium excretion was monitored over the following 2 h. Measurements of the filterability of aluminium from the rat plasma, and the glomerular filtration rate (inulin clearance), enabled us to calculate the filtered load of aluminium, and hence determine aluminium reabsorption. At all doses of administered aluminium, that administered as sulphate was excreted less effectively than that administered as citrate. This difference was attributable to the much greater filterability of aluminium administered as citrate. However, for any given filtered load, the excretion of aluminium administered as citrate was not significantly different (in either fractional or absolute terms) from the excretion of aluminium administered as sulphate. It seems likely that, following aluminium sulphate administration, the filtered aluminium may be an aluminium citrate form which is then reabsorbed in the same way as aluminium administered as citrate. It is thus apparent that aluminium removal from the body could be further enhanced if it were possible to prevent the tubular reabsorption of the aluminium species which is so effectively filtered following aluminium citrate administration.
Department of Physiology, Medical School, University of Birmingham, UK.
C J
CJ
Lote
J A
JA
Wood
A
A
Thewles
M
M
Freeman
D000042:Absorption; D000534:Alum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000535:Aluminum / Q000097:blood / Q000652:urine*; D000818:Animals; D002951:Citrates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019343:Citric Acid; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013054:Spectrophotometry, Atomic; D013329:Structure-Activity Relationship
D000534:Alum Compounds; D002951:Citrates; D019343:Citric Acid; C041524:aluminum sulfate; D000535:Aluminum