Bone aluminum uptake in uremic rats receiving intraperitoneal iron.

To assess the effect of concomitant iron and aluminum loads on bone aluminum accumulation and on the response to the deferoxamine test in rats with the same aluminum surcharge, Wistar rats with chronic renal failure were divided into three groups: iron-overloaded rats (N = 6) (intraperitoneal iron); iron-depleted rats (N = 6) (blood withdrawal two to three times per week); control rats (N = 4) (no manipulation). All groups received intraperitoneal aluminum simultaneously. After 6 wk, a deferoxamine challenge test was performed. Thereafter, bone aluminum and iron were measured. The iron-overloaded rats showed higher bone iron content (iron overloaded: 147.7+/-55.4 microg/g; iron depleted: 7.9+/-1.0, and controls 13.3+/-9.9 microg/g, p < 0.010) and lower bone aluminum content (iron overloaded: 14.2+/-4.0 microg/g; iron depleted: 70.9+/-35.1 microg/g; controls: 72.7+/-28.3 microg/g p < 0.005). No differences were found between the iron-depleted and control rats. After the deferoxamine infusion, the iron-depleted rats tended to have higher serum aluminum increments (p = NS) and higher urinary aluminum excretion (p < 0.012, p < 0.020) than control rats despite similar amounts of aluminum in bone of the two groups. Aluminum bone accumulation was minor if iron and aluminum loads were given concomitantly. The iron depletion influenced the results of the deferoxamine challenge test in rats with similar bone aluminum burden.

Role of iron metabolism in absorption and cellular uptake of aluminum.

The effect of iron status on aluminum (Al) absorption was investigated in this study in vivo using an animal model and in vitro using an intestinal mucosal cell line. In the in vivo model rats were rendered iron overloaded by intraperitoneal injection of iron dextran (5 mg/48 hr) or iron deficient by phlebotomy (2.5 to 3 ml blood/week). These rats, and normal controls, were then dosed with Al(OH)3 (40 mg/day) for 30 days. Urinary excretion of Al was significantly greater in the iron deficient group than in the other two groups throughout the study period, and brain Al at the end of the experiment was significantly increased in the iron depleted group (1.93 micrograms/g) and decreased in the iron overloaded group (0.73 microgram/g) compared with controls (1.42 micrograms/g). The brain Al levels in iron overloaded rats were no higher than those in normal rats that had not been dosed with Al(OH)3 (0.61 microgram/g). No significant differences were found in serum Al levels. In the in vitro experiments cultures of the rat intestinal cell line RIE1 were iron overloaded by addition of iron nitrilotriacetate (0.1 mM) or iron depleted with desferrioxamine (5 micrograms/ml) for 20 days prior to pulsing with Al transferrin (0.5 mg/ml) for 24 hours. Uptake of Al was significantly greater in the iron depleted cells (2.3 ng/micrograms cell DNA) than in iron overloaded (0.81 ng) or untreated (0.83 microgram) cells. These studies show that iron depletion markedly increases absorption and cellular uptake and suggest that susceptible individuals, such as renal failure patients, run an increased risk of toxicity if they are iron deficient.

Iron uptake in aluminium overload: in vivo and in vitro studies.

In this study we have evaluated the haematological consequences of chronic aluminium (Al) overload. We have also investigated 'in vivo' whether aluminium overload may modulate gastrointestinal iron (Fe) absorption and 'in vitro' whether the presence of aluminium may influence the cellular uptake of iron. The in vivo studies were performed in rats with normal renal function and the in vitro experiments were done using the rat intestinal epithelial cell line RIE-1. The results demonstrate that aluminium deposit in tissues even with normal renal function. The intraperitoneal aluminium loading resulted in serum and tissue aluminium increases comparable with concentrations found in aluminium-intoxicated renal patients. The aluminium intoxication was accompanied by a microcytic anaemia with a haematological pattern similar to that observed in iron-deficiency anaemia. Nevertheless, iron absorption was significantly reduced despite an increased total iron binding capacity (TIBC). In addition, aluminium was also able to reduce in vitro cellular uptake of iron in the RIE-1 intestinal cell line. These experimental results demonstrate that aluminium interferes with iron absorption and iron transfer, and suggest that these mechanisms may be responsible for maintaining and even increasing the anaemia observed in aluminium overload.