Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate

D. Froment Ph., Bruce Molitoris, B. Buddington, N. Miller, A. C. Alfrey

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

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°C vs. 4°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.

Original languageEnglish (US)
Pages (from-to)978-984
Number of pages7
JournalKidney International
Volume36
Issue number6
StatePublished - 1989
Externally publishedYes

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Aluminum
Tight Junctions
Ruthenium Red
aluminum citrate
Gastrointestinal Absorption
Glucose
Goblet Cells
Intestinal Absorption
Extracellular Space
Citric Acid
Sprague Dawley Rats
Gastrointestinal Tract
Calcium
Temperature

ASJC Scopus subject areas

  • Nephrology

Cite this

Froment Ph., D., Molitoris, B., Buddington, B., Miller, N., & Alfrey, A. C. (1989). Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate. Kidney International, 36(6), 978-984.

Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate. / Froment Ph., D.; Molitoris, Bruce; Buddington, B.; Miller, N.; Alfrey, A. C.

In: Kidney International, Vol. 36, No. 6, 1989, p. 978-984.

Research output: Contribution to journalArticle

Froment Ph., D, Molitoris, B, Buddington, B, Miller, N & Alfrey, AC 1989, 'Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate', Kidney International, vol. 36, no. 6, pp. 978-984.
Froment Ph., D. ; Molitoris, Bruce ; Buddington, B. ; Miller, N. ; Alfrey, A. C. / Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate. In: Kidney International. 1989 ; Vol. 36, No. 6. pp. 978-984.
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abstract = "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°C vs. 4°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.",
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