ULTRASENSITIVE ANALYSIS OF THE INTESTINAL-ABSORPTION AND COMPARTMENTALIZATION OF ALUMINUM IN UREMIC RATS - A AL-26 TRACER STUDY EMPLOYING ACCELERATOR MASS-SPECTROMETRY

Background. Developments in accelerator mass spectrometry (AMS) now pe rmit the determination of femtogram amounts of Al-26 in blood and in v arious tissues with good precision and free of external contamination. Methods. In the present study we used trace quantities of Al-26 to in vestigate the intestinal absorption and compartmentalization of alumin ium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair-fed c ontrols (C). Single oral doses of 20 ng Al-26 were administered to six animals in each group and, subsequently, 24-h post-load Al-26 was ana lysed in serum, urine, bone, liver, and spleen by means of AMS. Result s. Serum concentrations of Al-26 were significantly lower in uraemic r ats compared to controls, whereas urinary excretion was comparable (Nx , 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a highe r fraction of ultrafiltrable serum Al-26 in uraemia. The target tissue s of cellular transferrin-mediated Al-26 uptake, liver and sleen, tend ed to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25+/- 0.27 pg/g respectively). In contrast, in bone, a site of extr acellular aluminium deposition, Al-26 concentrations were more elevate d in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total Al-26 accumulation in all measured target tissues was significan tly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of Al-26 from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. Conclusions. Our data suggest that fractional absorption from a dietary level dose of Al-26 is about 0.13%. Compartmentalization occurs in transferrin-de pendent target tissues such as liver and spleen; however, in quantitat ive terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmenta lization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellula r accumulation of aluminium in liver and spleen.