Kinetics for the synthetic bile acid 75selenohomocholic acid-taurine in humans: Comparison with [14C]taurocholate

Jazrawi, R. P.; Ferraris, R.; Bridges, C.; Northfield, T.C.

doi:10.1016/0016-5085(88)90306-x

Cited by 25 publications

(13 citation statements)

References 14 publications

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“…So the observations of Jazrawi et al [12] seem to be complementary to the results in this study. Another study on the stability of 75SeHCAT toward enzymatic hydrolysis [14] also re ports breakdown of this compound to an extent of at least 75% by certain strains of anaerobic bacteria from human feces, a ma jor product of degradation being 75SeHCA.…”

Section: Discussionsupporting

confidence: 51%

“…As there is little chance for passive ab sorption in the colon and return to the pool of the deconjugated compound, it is clear that the deconjugation was only detected as a minor process by Jazrawi et al [12]. So the observations of Jazrawi et al [12] seem to be complementary to the results in this study.…”

Section: Discussioncontrasting

confidence: 50%

“…Jazrawi et al [12], however, reported re cently a relative minor deconjugation of 75SeHCAT in man. This conclusion was based on the analysis of the bile acid pool for 75SeHCA reconjugation with glycine.…”

Section: Discussionmentioning

confidence: 99%

“…The in vivo behavior of 75SeHCAT has also been evaluated in a group of 5 normal volunteers by Jazrawi et al [12]. These au thors found a comparable 'apparent frac tional turnover rate' for 14C-TCA and 75SeH-CAT.…”

mentioning

confidence: 91%

“…Structural considerations together with biological tests led to the selection of the present compound 75SeHCAT out of a series of 75Se-containing bile acid analogues syn thesized [7], Studies have been reported where the be havior of the bile acid analogue 75SeHCAT was compared with that of l4C-taurocholate [11,12]. With exception of the l4C isotope at the 24 position, the 14C-labeled bile acids are chemically identical to their physiological counterparts.…”

mentioning

confidence: 99%

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[<sup>75</sup>Se]-Selenohomotaurocholic Acid Degradation by Bacterial Enzymes in vitro and in vivo

Berg

Rooij²,

Bosman‐Jacobs³

1990

Digestion

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The stability of the bile acid analogue [⁷⁵Se]-selenohomotaurocholic acid (⁷⁵SeH-CAT) was studied in man. When ⁷⁵SeHCAT was administered to patients for diagnostic purposes the majority of labeled material present in the feces was found deconjugated. In vitro incubation of ⁷⁵SeHCAT, by addition of fecal homogenate or with addition of purified enzyme, showed identical deconjugation. The relative differences in polarities of ⁷⁵SeHCAT, [⁷⁵Se]-selenohomocholic acid (⁷⁵SeHCA), [¹⁴C]-taurocholic acid (¹⁴C-TCA) and [¹⁴C]-cholic acid (¹⁴C-CA) were estimated by isoelectric focusing and selective chloroform extractions at various pH values. The pi values representing the pH where these molecules become uncharged were for ⁷⁵SeHCA and ⁷⁵SeHCAT 3.1, for ¹⁴C-TCA 3.0 and for ¹⁴C-CA 3.9. These results suggest that from these bile acids only ¹⁴C-CA is a candidate for passive absorption in the colon, while ⁷⁵SeHCA would be far too polar for passive diffusion. Indeed, we could demonstrate the inability of ⁷⁵SeHCA for passive absorption in healthy persons. In conclusion, ⁷⁵SeHCAT, specifically selected to monitor active ileal bile acid transport, functions as a good indicator of this process in its conjugated form. In contrast to published data it is susceptible to bacterial degradation, and therefore gives rise to a diminished whole-body retention.

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Section: Discussionsupporting

confidence: 51%

Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

mentioning

confidence: 99%

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[<sup>75</sup>Se]-Selenohomotaurocholic Acid Degradation by Bacterial Enzymes in vitro and in vivo

Berg

Rooij²,

Bosman‐Jacobs³

1990

Digestion

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Effect of chronic administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acids in man

et al. 1990

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The effect of long-term administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acids was determined using the tauro 23 (75Se) selena-25 homotaurocholic acid test in a controlled double-blind study involving healthy subjects (n = 15). Subjects received placebo or 13 to 15 mg/kg/day ursodeoxycholic acid for 5 wk. In the placebo group (n = 7) there was no change in the composition of serum bile acids or in the mean percentage of retention of tauro 23(75Se) selena-25 homotaurocholic acid (36.1% +/- 6.0% vs. 38.7% +/- 6.7%). In contrast, in the ursodeoxycholic acid group, serum ursodeoxycholic acid conjugates increased and the percentage of retention of tauro 23 (75Se) selena-25 homotaurocholic acid fell from 45.8% +/- 6.8% to 20.5% +/- 5.7% (p less than 0.01). We conclude that ursodeoxycholic acid administration reduces ileal absorption of endogenous bile acids. These findings provide a rational explanation for the changes in the composition of the bile acid pool during ursodeoxycholic acid therapy and could have important therapeutic implications.

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Bile Acid Diarrhea and NAFLD: Shared Pathways for Distinct Phenotypes

et al. 2020

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Irritable bowel syndrome with diarrhea (IBS‐D) and NAFLD are both common conditions that may be influenced by shared pathways of altered bile acid (BA) signaling and homeostatic regulation. Pathophysiological links between IBS‐D and altered BA metabolism include altered signaling through the ileal enterokine and fibroblast growth factor 19 (FGF19) as well as increased circulating levels of 7α‐hydroxy‐4‐cholesten‐3‐one, a metabolic intermediate that denotes increased hepatic BA production from cholesterol. Defective production or release of FGF19 is associated with increased BA production and BA diarrhea in some IBS‐D patients. FGF19 functions as a negative regulator of hepatic cholesterol 7α‐hydroxylase; therefore, reduced serum FGF19 effectively de‐represses hepatic BA production in a subset of IBS‐D patients, causing BA diarrhea. In addition, FGF19 modulates hepatic metabolic homeostatic response signaling by means of the fibroblast growth factor receptor 4/klotho beta receptor to activate cascades involved in hepatic lipogenesis, fatty acid oxidation, and insulin sensitivity. Emerging evidence of low circulating FGF19 levels in subsets of patients with pediatric and adult NAFLD demonstrates altered enterohepatic BA homeostasis in NAFLD. Conclusion: Here we outline how understanding of shared pathways of aberrant BA homeostatic signaling may guide targeted therapies in some patients with IBS‐D and subsets of patients with NAFLD.

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Kinetics for the synthetic bile acid 75selenohomocholic acid-taurine in humans: Comparison with [14C]taurocholate

Cited by 25 publications

References 14 publications

[<sup>75</sup>Se]-Selenohomotaurocholic Acid Degradation by Bacterial Enzymes in vitro and in vivo

[<sup>75</sup>Se]-Selenohomotaurocholic Acid Degradation by Bacterial Enzymes in vitro and in vivo

Effect of chronic administration of ursodeoxycholic acid on the ileal absorption of endogenous bile acids in man

Bile Acid Diarrhea and NAFLD: Shared Pathways for Distinct Phenotypes

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