Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate.
Clinical and experimental studies have shown that citrate markedly enhances the intestinal absorption of aluminum (Al), but the site and mechanism of enhanced absorption are unknown. To determine where in the gastrointestinal tract aluminum citrate (Alcitr) was absorbed. Alcitr was gavaged with D-[1-3H] glucose in male Sprague-Dawley rats. Plasma Al levels increased rapidly and simultaneously peaked with D-[1-3G] glucose, suggesting early proximal bowel absorption. In in vitro duodenal and jejunal everted gut preparations, Alcitr incubation resulted in increased tissue Al levels and markedly enhanced transmural transport of Al and citr. Unlike citr, the transmural movement of Al was independent of temperature (37 degrees C vs. 4 degrees C). On the other hand, Al lactate (al Lac) increased tissue associated Al levels but had no effect on transmural Al movement. To determine if this large flux of Al following Alcitr administration was due to paracellular movement, ruthenium red and Ussing chamber studies were used to evaluate the morphologic and functional integrity of cellular tight junctions. Alcitr, as opposed to AlCl3, markedly increased ruthenium red deposits in intercellular spaces, especially around goblet cells, and induced a prolonged significant reduction in transmural resistance. Alcitr also resulted in rapid and nearly complete (99.7%) chelation of free calcium, an event known to disrupt cellular tight junction integrity. Taken together, these data suggest that enhanced Al absorption following administration of Alcitr occurs in the proximal bowel via the paracellular pathway due to the opening of cellular tight junctions.
Froment
D P
DP
Department of Medicine, Veterans Administration Medical Center, Denver, Colorado.
Molitoris
B A
BA
Buddington
B
B
Miller
N
N
Alfrey
A C
AC
D000535:Aluminum / Q000493:pharmacokinetics*; D000818:Animals; D002951:Citrates / Q000493:pharmacokinetics / Q000494:pharmacology*; D019343:Citric Acid; D004357:Drug Synergism; D004386:Duodenum / Q000502:physiology; D007365:Intercellular Junctions / Q000502:physiology; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002951:Citrates; D019343:Citric Acid; D000535:Aluminum