Mechanisms of aluminum absorption in rats

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Aluminum has become a dietary toxin in modern times but its mechanism of absorption is poorly understood. After ingestion, the systemic transfer of aluminum is small but it is greatly affected by the coingestion of certain dietary agents, such as citrate, that complex with the metal in the intestinal lumen or transiently alter the permeability of the mucosa. Here, mechanisms of aluminum absorption were studied by using freshly prepared aluminum hydroxide and aluminum citrate. Everted sacs of rat gut were used to investigate the site of absorption, effect of chemical charge on absorption of aluminum citrate, and presence of active or passive absorption with use of the metabolic inhibitor ouabain. Absorption was biphasic with a large tissue uptake that was consistent with adhesion to mucus-mucosal surface but little tissue transport, which was consistent with passive paracellular permeation. Citrate reduced the uptake-transport ratio both by competing with the mucosal uptake and by increasing mucus-mucosal permeation but not by affecting the charge of the luminal aluminum species. Despite the potential for hydroxypolymerization of aluminum at intestinal pH, the small bowel and colon absorbed aluminum passively and paracellularly but the stomach did not. The predominantly proximal absorption of aluminum observed in vivo is a reflection of the proximal absorption, and therefore removal, of dietary constituents (eg, citrate) that enhance mucosal permeation of aluminum. The colon should be investigated further as a site of significant paracellular permeability.