Duodenal Glucuronide Synthesis. III. Identification of Phenolphthalein Glucuronide as a Conjugation Product of Phenolphthalein in the Intestinal Tract in Rat.

Lehtinen, Anita; Savola, Petter; Pulkkinen, M.O.; Hartiala, K.; Veige, S.; Diczfalusy, E.

doi:10.3891/acta.chem.scand.12-1592

Cited by 9 publications

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“…There is also some direct evidence of intestinal glucuronidation of laxative diphenols. Thus Lehtinen et al (1958) showed that a glucuronide is formed when phenolphthalein is incubated with rat duodenal tissue slices; and Vogt et a/. (1965) demonstrated that mucosal scrapings of the rat small intestine can release a conjugate when incubated with desacetylbisacodyl.…”

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Uptake, Conjugation and Transport of Laxative Diphenols by Everted Sacs of the Rat Jejunum and Stripped Colon

Sund

Hillestad

1982

Acta Pharmacologica et Toxicologica

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Phenolphthalein (PHEN), desacetylbisacodyl (DES) and oxyphenisatin (OXY) were incubated with everted sacs of the rat jejunum and stripped descending colon; the mucosal and serosal fluid were analysed with respect to free and conjugated diphenol by means of HPLC. Conjugates were measured as the amount of free diphenol in completely hydrolyzed samples less the amount before hydrolysis. A study with double‐sided administration of PHEN revealed that diphenol uptake from and conjugate output to both sides followed a rectilinear course for 15–90 min. A standard incubation time of 60 min. was chosen for the subsequent experiments, in which the diphenols were administered at the mucosal side at a low and a high concentration. Diphenol uptake, i.e. the amount of free diphenol administered less the amount recovered at the mucosal side, varied in an order (PHEN>DES>OXY) which seems to be inversely related to the order of water solubility of the compounds. Tissue accumulation and conjugate output relative to uptake varied with the dose, and from one compound to another. At low initial concentration (20 nmol/ml), the compounds were transferred to the jejunal and colonic serosal fluid almost entirely as conjugates (≥95%); the transfer rates followed, qualitatively, the same order as above. In jejunum, more conjugates were released to the mucosal than to the serosal side; in colon the distribution was reversed. Increasing the dose to 100 nmol/ml caused a corresponding increase in uptake, but relative output decreased and tissue accumulation increased; thus demonstrating capacity limitation. With PHEN, the ratio of conjugated:free diphenol on the serosal side remained essentially unchanged; with DES in particular, but also with OXY the ratio decreased. These findings may be interpreted to mean that in case of PHEN capacity limitation is linked to conjugate efflux, while DES and OXY may be poor substrates for glucuronide formation as well. Experiments with serosal side administration like the double‐sided PHEN experiments verified the dissimilar conjugate distribution in jejunal and colonic sacs; the phenomenon is to some extent discussed in the text. Identity tests gave evidence that the conjugates were mainly monoglucuronides.

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confidence: 99%

Uptake, Conjugation and Transport of Laxative Diphenols by Everted Sacs of the Rat Jejunum and Stripped Colon

Sund

Hillestad

1982

Acta Pharmacologica et Toxicologica

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Metabolism of Foreign Substances in the Gastrointestinal Tract

Hartiala

1977

Comprehensive Physiology

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The sections in this article are: Foreign Substance Metabolism by the Intestinal Mucosa Nonsynthetic Reactions Synthetic Reactions Multiplicity of Biotransformation Reactions Species and Strain Differences Fetal Development and Phylogenetic Aspects Biotransformation by Intestinal Microorganisms Adaptation of Xenobiotic Metabolism in the Gastrointestinal Tract Endogenous Compounds in Regulation of Drug Metabolism Enhancement of Biotransformation by Exogenous Compounds Effect of Luminal Contents Interaction of Intestinal Microflora and Mucosal Functions Concluding Remarks

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Comparison of phenolphthalein and phenolphthalein glucuronide on net water transport in rat ileum and colon

1983

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Phenolphthalein is an odorless, tasteless compound, poorly soluble in water, but readily soluble in alcohol or ether. Although its laxative activity was discovered in 1902, the mechanism of action remains unclear. Phenolphthalein has been found to be an ineffective laxative in both jaundiced patients and in experimental animals with ligated common bile ducts. In contrast to the poor solubility of phenolphthalein, phenolphthalein glucuronide is highly water-soluble. In addition, phenolphthalein glucuronide is found in bile following oral phenolphthalein administration, suggesting an enterohepatic circulation. We compared the effect of phenolphthalein and phenolphthalein glucuronide on net water absorption of the ileum and colon of Sprague-Dawley rats using a single-pass perfusion technique. Perfusion of phenolphthalein (10 mg/dl in 154 mM NaCl with 0.5% ethanol and 0.1 g/l gum arabic) resulted in significantly reduced water absorption in both the ileum and colon (66% and 64%, respectively, P less than 0.05). In contrast, phenolphthalein glucuronide did not have a significant effect on net water flux compared to control perfusion in either the ileum or colon. In the ileum only 77 +/- 3% and colon 71 +/- 1.2% of the phenolphthalein infused was recovered, suggesting that much of the infused phenolphthalein was absorbed. In contrast there was no evidence of absorption of phenolphthalein glucuronide, as 98.9 +/- 1.2% was recovered from ileal and colon perfusions. Phenolphthalein glucuronide is not the active form of phenolphthalein, although it may be an effective laxative after deconjugation by colonic bacteria.

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Duodenal Glucuronide Synthesis. III. Identification of Phenolphthalein Glucuronide as a Conjugation Product of Phenolphthalein in the Intestinal Tract in Rat.

Cited by 9 publications

References 0 publications

Uptake, Conjugation and Transport of Laxative Diphenols by Everted Sacs of the Rat Jejunum and Stripped Colon

Uptake, Conjugation and Transport of Laxative Diphenols by Everted Sacs of the Rat Jejunum and Stripped Colon

Metabolism of Foreign Substances in the Gastrointestinal Tract

Comparison of phenolphthalein and phenolphthalein glucuronide on net water transport in rat ileum and colon

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