EFFECT OF IRON STATUS ON THE INTESTINAL-ABSORPTION OF ALUMINUM - A REAPPRAISAL

Clinical and experimental studies have shown that serum aluminum (Al) is bound to transferrin and that cellular uptake of Al appears to be m ediated by transferrin receptors. Based on these findings it is widely believed that intestinal Al absorption occurs via iron-specific, tran sferrin-dependent pathways and that iron (Fe) deficiency increases the intestinal absorption of Al. However, since no transferrin receptors are expressed on the absorptive surface of small intestinal epithelial cells this notion is doubtful. To further clarify the issue the prese nt study investigated the effect of marked alterations of body Fe stor es on the intestinal absorption of Al using three different rat models . (I) Serum Al concentrations and urinary excretion rates of Al were m easured in iron-overloaded (Fe+) or iron-deficient (Fe-) rats with eit her normal (C) or impaired (5/6 nephrectomy) renal function (Nx) emplo ying oral Al loads in single dose studies. (II) Tissue Al accumulation as well as serum and urine Al were determined in respective experimen tal groups exposed to a prolonged (41 days) dietary Al load. (III) To assess the effect of Fe status on the intestinal absorption of Al dire ctly at the organ level perfusions of in situ rat gut preparations wer e performed. In the single dose studies administration of Al resulted in similar urinary excretion rates of Al in intact kidney groups (C+Fe -, 229 +/- 85 nmol/5 days; C+Fe+, 240 +/- 59 nmol/5 day;) despite mark ed differences in liver Fe (C+Fe-, 1.34 +/- 0.16 vs. C+Fe+, 55.69 +/- 13.20 mu mol/g) and duodenal mucosal Fe (C+Fe-, 0.68 +/- 0.11 vs. C+Fe +, 3.17 +/- 0.82 mu mol/g). In addition, mucosal Al concentration 24 h ours after the load was not affected by the Fe status (C+Fe-, 37 +/- 1 6 nmol/g, C+Fe+, 56 +/- 19 nmol/g). Regardless of the Fe status post-l oad AI excretion was enhanced in Nx rats (Nx+Fe-, 533 +/- 234 nmol/fiv e days, Nx+Fe+, 536 +/- 201 nmol/five days). Irrespective of Fe status a prolonged dietary Al load resulted in a similar increase in tissue Al concentration (nmol/g) in liver (baseline, 159 +/- 22; C+Fe-, 276 /- 125; C+Fe+, 251 +/- 71; Nx+Fe-, 330 +/- 119; Nx+Fe+, 437 +/- 67) an d in bone (baseline, 219 +/- 119; C+Fe-, 433 +/- 174, C+Fe+, 485 +/- 1 41; Nx+Fe-, 504 +/- 185; Nx+Fe+, 548 +/- 215). The increase in spleen Al was significantly larger in Fe-overloaded rats (baseline, 194 +/- 2 0; C+Fe+, 511 +/- 129 vs. C+Fe-, 308 +/- 62, P < 0.05; Nx+Fe+, 514 +/- 67 vs. Nx+Fe-, 389 +/- 119, P < 0.05). Brain Al tended to rise in Nx rats only (baseline, 96 +/- 33; Nx+Fe+, 174 +/- 100, Nx+Fe-, 156 +/- 7 8, P = NS). Analogous results were obtained in in situ intestinal perf usion studies: Fe deficiency and Fe overload both did not affect the t ime-dependent increase in serum Al in either systemic or portal vein b lood. When paracellular intestinal permeability was assessed mannitol absorption was significantly higher in uremic animals as compared to c ontrols. Pharmacological blockade (2 mM kinetin) of the paracellular p ermeability substantially reduced the time-dependent increase in serum Al in uremic rats but had little effect in control animals, suggestin g that even the excess absorption of Al observed in uremia occurs via a paracellular rather than an iron-specific pathway. In conclusion, th e findings of the present study provide several lines of evidence agai nst the commonly accepted view that the intestinal absorption of Al oc curs via iron-specific pathways. Most likely, this is related to the f act, that neither the absorption of Fe nor the absorption of Al are me diated via transferrin receptors. In addition, the enhanced intestinal absorption of Al observed in uremic rats does also not occur via iron -specific pathways, but seems to be due to increased paracellular perm eability of the intestine.