The effect of desferrioxamine on tissue aluminum concentration and bone histology in aluminum-loaded rats with renal failure.
Aluminum (Al) intoxication is a condition that reponds well to treatment with desferrioxamine (DFO) in humans with renal failure. The present study deals with the effect of DFO administration on the Al concentrations of different tissues and on bone histology in rats with renal failure, loaded with Al. After the Al-loading there is an important increase of Al in serum, (1,103 +/- 355 micrograms/l) (mean +/- SD), bone (116 +/- 14 mg/kg), liver 238 +/- 78 mg/kg) and muscle (8.5 +/- 4.1 mg/kg). Urinary Al excretion averages 287 +/- 68 micrograms/d. Serum biochemistry reveals renal failure and hypercalcemia (3.5 +/- 0.3 mmol/l). The rats were subsequently treated by either placebo or 150 mg DFO per week. The placebo-treated rats show a spontaneous decrease of serum Ca and Al and of liver and muscle Al content. The DFO-treated rats had, compared to the placebo-treated animals, an increase of urinary Al excretion and lower Al concentration in bone and brain. Bone histology after Al-loading shows an increase in osteoid measurement when compared with non-Al-loaded animals with renal failure: osteoid volume 25.6 +/- 13.3% versus 5.0 +/- 2.9% and osteoid index 63.6 +/- 22.1% versus 27.3 +/- 15.3% in Al-loaded and non-Al-loaded animals, respectively. In addition, the aluminon stain covered 89.7 +/- 3.8% of the bone trabeculae of Al-loaded rats. Under placebo treatment the osteoid measurements increase, reflecting a worsening of Al-induced bone disease. DFO therapy did not result in a significant change of the different measurements of bone histology, despite the decrease of aluminon staining to 67.7 +/- 13.7%.(ABSTRACT TRUNCATED AT 250 WORDS)
Verbeelen
D
D
Department of Medicine, Academisch Ziekenuis, Brussel, Belgium.
Smeyers-Verbeke
J
J
van Hooff
I
I
de Roy
G
G
D000535:Aluminum / Q000493:pharmacokinetics* / Q000506:poisoning*; D000818:Animals; D001847:Bone Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011041:Poisoning / Q000188:drug therapy; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution / Q000502:physiology
D000535:Aluminum; D003676:Deferoxamine