Factors Affecting Plasma Clearance of [14C]Cholic Acid in Patients with Cirrhosis

1973 ◽  
Vol 45 (2) ◽  
pp. 147-161 ◽  
Author(s):  
M. D. Kaye ◽  
J. E. Struthers ◽  
J. S. Tidball ◽  
Elizabeth DeNiro ◽  
F. Kern
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Normal Subjects ◽  
Systemic Circulation ◽  
Duodenal Juice ◽  
Factors Affecting ◽  
Acid Injection ◽  
Cirrhotic Patients ◽  
Conjugated Bile Acids

1. Clearance of [14C]cholic acid from the systemic circulation was studied in six normal subjects and eight patients with biopsy-proven hepatic cirrhosis. In both groups, during fasting, the curve for disappearance of radioactivity from the serum during the first 100 min after [14C]cholic acid injection was double-exponential in form. During the early phase, clearance was significantly more rapid, and concentrations of conjugated and free bile acid were significantly lower, in normals than in cirrhotics. 2. Radioactivity disappeared from the systemic circulation of normals within 3 h, and neither intravenous cholecystokinin nor the ingestion of food influenced serum radioactivity. Almost all cirrhotic patients had ‘spontaneous’ rises in serum radioactivity, which began approximately 2 h after [14C]cholic acid injection. Cholecystokinin or food given 4–8 h after [14C]cholic acid administration, produced rises. Continuous aspiration of duodenal juice markedly reduced these rises. Reinfusion of duodenal juice into the upper intestine was followed by a rise in serum radioactivity. 3. All rises were due, almost exclusively, to conjugated bile acids. 4. Impaired bile acid clearance in cirrhotics may result from inefficient hepatic extraction of bile acids, increased leakage of conjugated bile acids from hepatic cells and shunting from portal to systemic circulations. The latter factor is probably responsible for elevated, fluctuating, plasma bile acid concentrations in cirrhotic patients.

EFFECTS OF ADRENALECTOMY AND CORTICOID REPLACEMENT ON BILE ACID CONJUGATION IN BILE FISTULA RATS

1963 ◽  
Vol 43 (2) ◽  
pp. 305-310 ◽  
Author(s):  
Kjell Hellström ◽  
Ove Strand
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
The Other ◽  
Bile Fistula ◽  
Adrenalectomized Rats ◽  
Conjugated Bile Acids ◽  
Fistula Bile

ABSTRACT Bile fistula bile from male normal, sham-operated, adrenalectomized and cortisone substituted adrenalectomized rats was analyzed for free and conjugated bile acids. 40–50 per cent of the bile acids from adrenalectomized rats were conjugated with glycine as compared to less than 10 per cent in the other groups. The cortisone substituted adrenalectomized rats showed a lower glycine conjugation than normal rats. In the bile from adrenal-ectomized rats, free cholic acid corresponding to 2–5% of the conjugated bile acids was detected. In the bile from the other groups less than 1% of free cholic acid was found. The mechanism responsible for the abnormal conjugation pattern found in adrenalectomized rats is discussed.

scholarly journals Biochemical aspects of malabsorption in marasmus

1984 ◽  
Vol 51 (1) ◽  
pp. 1-6 ◽  
Author(s):  
H. C. Mehta ◽  
A. S. Saini ◽  
Harjit Singh ◽  
P. S. Dhatt
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Bile Salts ◽  
Duodenal Juice ◽  
Fat Absorption ◽  
Bacterial Counts ◽  
Free Bile Acids ◽  
Normal Controls ◽  
Conjugated Bile Acids

1. Sixty marasmic children and fifteen normal age-matched controls were investigated for the absorption of fats and proteins. Their duodenal juice samples were also analysed for bile salts and microflora.2. A significant amount of malabsorption, with respect to both the dietary ingredients, was observed in the majority of the marasmic children.3. The levels of conjugated bile acids in the duodenal juice samples of marasmic children were significantly lower as compared with those of normal controls, while the reverse was true for free bile acids and bacterial counts.4. Significant correlations were observed between bile acid levels and fat absorption and also between microflora and free bile acids.5. The pathophysiology of malabsorption in marasmus is discussed in the light of these findings.

Radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid from human serum, with use of 125I-labeled ligands.

1979 ◽  
Vol 25 (2) ◽  
pp. 264-268 ◽  
Author(s):  
O Mäentausta ◽  
O Jänne
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Chenodeoxycholic Acid ◽  
Deoxycholic Acid ◽  
Serum Samples ◽  
Analytical Recovery ◽  
Hepatobiliary Diseases ◽  
Polyethylene Glycol Precipitation ◽  
Free Serum

Abstract We describe a method for radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid in serum. In the method, 125I-labeled bile acid conjugates are used as the tracers along with antibodies raised against individual bile acid-bovine serum albumin conjugates. Antibody-bound and free bile acids were separated by polyethylene glycol precipitation (final concentration, 125 g/L). Before radioimmunoassay, 0.1-mL serum samples were precipitated with nine volumes of ethanol, and portions from the supernate were used in the assays. The lowest measurable amounts of the bile acids, expressed as pmol/tube, were: cholic acid conjugates, 2; chenodeoxycholic acid conjugates, 0.5; and deoxycholic acid conjugates. 2. Analytical recovery of bile acids added to bile acid-free serum ranged from 85 to 110%; intra-assay and inter-assay CVs ranged from 3.2 to 5.3% and from 5.3 to 12.2%, respectively. Concentrations (mean +/- SD) of the bile acid conjugates in serum from apparently healthy women and men (in mumol/L) were: cholic acid conjugates, 0.43 +/- 0.17 (n = 126); chenodeoxycholic acid conjugates, 0.47 +/- 0.23 (n = 111); and deoxycholic acid conjugates, 0.33 +/- 0.11 (n = 96). The values for primary bile acids were greatly increased in patients with various hepatobiliary diseases.

Interaction between bile acids and staphylococcal polysaccharide: inhibition of capsule formation in encapsulated mutant strains (taurine+, taurine−) of Staphylococcus aureus

1983 ◽  
Vol 29 (12) ◽  
pp. 1653-1660 ◽  
Author(s):  
Toshichika Ohtomo
Keyword(s):  
Staphylococcus Aureus ◽  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Taurocholic Acid ◽  
Polysaccharide Antigen ◽  
Capsule Formation ◽  
Mutant Strains ◽  
Bile Acid Derivatives ◽  
Capsular Material

In a previous paper, we showed that bile acid derivatives inhibit capsule formation as well as taurine biosynthesis in a taurine+ (Tau+) encapsulated strain of Staphylococcus aureus. In the present study, binding of [14C]cholic acid ([14C]CA) and [14C]taurocholic acid ([14C]TA) to the staphylococcal polysaccharide antigen (SPA) of the capsular fraction was examined. The bile acids were found to bind with SPA via taurine of the Tau+ cells. [14C]CA bound with the SPA fraction of the Tau+ strain within 10–30 min, whereas 60–120 min was required in the binding of [14C]TA. Various bile acids competed with cholic acid binding to Tau+ cells which was shown by the inhibition of binding with cholic acid or taurocholic acid but not with glycholic acid. Binding of bile acid derivatives to a Tau− encapsulated mutant or to capsular material from this mutant was not observed.

scholarly journals Bile Acid Uptake Transporters as Targets for Therapy

2017 ◽  
Vol 35 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Davor Slijepcevic ◽  
Stan F.J. van de Graaf
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Energy Homeostasis ◽  
Sodium Taurocholate ◽  
Hepatic Uptake ◽  
Farnesoid X Receptor ◽  
Acid Uptake ◽  
Bile Acid Uptake ◽  
Uptake Transporters ◽  
Conjugated Bile Acids

Background: Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids. Multiple ASBT-inhibitors are already in clinical trials to inhibit intestinal bile acid uptake. Here, we discuss current insights into the consequences of targeting bile acid uptake transporters on systemic and intestinal bile acid dynamics and discuss the possible therapeutic applications that evolve as a result.

scholarly journals Metabolism of Oxo-Bile Acids and Characterization of Recombinant 12α-Hydroxysteroid Dehydrogenases from Bile Acid 7α-Dehydroxylating Human Gut Bacteria

2018 ◽  
Vol 84 (10) ◽  
Author(s):  
Heidi Doden ◽  
Lina A. Sallam ◽  
Saravanan Devendran ◽  
Lindsey Ly ◽  
Greta Doden ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Deoxycholic Acid ◽  
Gut Bacteria ◽  
Dietary Lipids ◽  
Human Gut ◽  
Content Type ◽  
Low Activity

ABSTRACTBile acids are important cholesterol-derived nutrient signaling hormones, synthesized in the liver, that act as detergents to solubilize dietary lipids. Bile acid 7α-dehydroxylating gut bacteria generate the toxic bile acids deoxycholic acid and lithocholic acid from host bile acids. The ability of these bacteria to remove the 7-hydroxyl group is partially dependent on 7α-hydroxysteroid dehydrogenase (HSDH) activity, which reduces 7-oxo-bile acids generated by other gut bacteria. 3α-HSDH has an important enzymatic activity in the bile acid 7α-dehydroxylation pathway. 12α-HSDH activity has been reported for the low-activity bile acid 7α-dehydroxylating bacteriumClostridium leptum; however, this activity has not been reported for high-activity bile acid 7α-dehydroxylating bacteria, such asClostridium scindens,Clostridium hylemonae, andClostridium hiranonis. Here, we demonstrate that these strains express bile acid 12α-HSDH. The recombinant enzymes were characterized from each species and shown to preferentially reduce 12-oxolithocholic acid to deoxycholic acid, with low activity against 12-oxochenodeoxycholic acid and reduced activity when bile acids were conjugated to taurine or glycine. Phylogenetic analysis suggests that 12α-HSDH is widespread amongFirmicutes,Actinobacteriain theCoriobacteriaceaefamily, and human gutArchaea.IMPORTANCE12α-HSDH activity has been established in the medically important bile acid 7α-dehydroxylating bacteriaC. scindens,C. hiranonis, andC. hylemonae. Experiments with recombinant 12α-HSDHs from these strains are consistent with culture-based experiments that show a robust preference for 12-oxolithocholic acid over 12-oxochenodeoxycholic acid. Phylogenetic analysis identified novel members of the gut microbiome encoding 12α-HSDH. Future reengineering of 12α-HSDH enzymes to preferentially oxidize cholic acid may provide a means to industrially produce the therapeutic bile acid ursodeoxycholic acid. In addition, a cholic acid-specific 12α-HSDH expressed in the gut may be useful for the reduction in deoxycholic acid concentration, a bile acid implicated in cancers of the gastrointestinal (GI) tract.

Bile Acid Synthesis in the Developing Sheep Liver

1973 ◽  
Vol 45 (3) ◽  
pp. 403-406
Author(s):  
R. A. Smallwood ◽  
P. Jablonski ◽  
J. McK. Watts
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Placental Transfer ◽  
Umbilical Vein ◽  
Acid Synthesis ◽  
Taurocholic Acid ◽  
Secondary Bile Acid ◽  
Radioactive Label ◽  
Sheep Liver ◽  
Conjugated Bile Acids

1. [14C]Cholesterol was administered intravenously via the umbilical vein to foetal sheep in the latter half of gestation, and the incorporation of radioactive label into foetal bile acids was assessed. 2. After 4 days, 0·5–2% of the radioactive label was found in foetal bile. Seventy to eighty per cent of the radioactive label in foetal bile was present as [14C]taurocholic acid and [14C]taurochenodeoxycholic acid. The remainder was [14C]cholesterol. No radioactive label was found in taurodeoxycholic acid, or in any of the glycine-conjugated bile acids. 3. It is concluded that the foetal sheep liver in the second half of gestation synthesizes taurocholic acid and taurochenodeoxycholic acid. However, the secondary bile acid taurodeoxycholic acid and the glycine-conjugated bile acids, present in foetal bile, have been acquired by placental transfer from the mother.

scholarly journals Studies on the origin of biliary phospholipid. Effect of dehydrocholic acid and cholic acid infusions on hepatic and biliary phospholipids

1990 ◽  
Vol 270 (3) ◽  
pp. 691-695 ◽  
Author(s):  
F Chanussot ◽  
H Lafont ◽  
J Hauton ◽  
B Tuchweber ◽  
I Yousef
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Bile Flow ◽  
Normal Values ◽  
Specific Radioactivity ◽  
Regulatory Effect ◽  
Experimental Protocol ◽  
Dehydrocholic Acid ◽  
Cellular Organelles

The correlation between the secretion of biliary phospholipid (PL) and bile acid suggests a regulatory effect of bile acid on PL secretion. Bile acids may influence PL synthesis and/or the mobilization of a preformed PL pool. The objective of this study was to determine the contribution of these two sources to biliary PL, by using an experimental protocol in which dehydrocholic acid (DHCA) and cholic acid (CA) were infused to manipulate biliary PL secretion. In control rats, there was a steady state in bile flow. PL secretion and the biliary secretion of newly synthesized phosphatidylcholine (PC). The specific radioactivity of PC in bile was significantly higher than in plasma, microsomes and canalicular membranes. DHCA infusion decreased biliary PC secretion rate by 80%, and secretion returned to normal values at the transport maximum of CA. The specific radioactivity of biliary PC was decreased by 30% by DHCA infusion and reached normal values during CA infusion. There were no significant changes in the specific radioactivity of PC in plasma or cellular organelles during infusion of bile acids. These data indicate that: (1) newly synthesized PC contributes a small percentage to biliary PC; thus a preformed pool (microsomal and extrahepatic) is a major source of biliary PL; (2) the contribution of the extrahepatic pool to the biliary PL may be more important than the microsomal pool.

Radiolabelled Bile Acid Clearance in Control Subjects and Patients with Liver Disease

1979 ◽  
Vol 57 (6) ◽  
pp. 499-508 ◽  
Author(s):  
L. R. Engelking ◽  
S. Barnes ◽  
C. A. Dasher ◽  
D. C. Naftel ◽  
B. I. Hirschowitz
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Cholic Acid ◽  
Indirect Evidence ◽  
Normal Subjects ◽  
Serum Bile Acid ◽  
Tracer Injection ◽  
Bile Acid Concentration ◽  
Glycocholic Acid ◽  
Acid Clearance

1. The serum bile acid disappearances of tracer doses of [24-14C]cholic acid and [1-14C]-glycocholic acid were studied in eight normal subjects and 11 patients with chronic liver disease (with or without cholestasis) in order to determine the effect of liver disease on hepatic clearances, reflux of conjugated cholic acid and initial distribution volume of each tracer. 2. Total cholic acid clearance was significantly reduced from normal (7·2 ± 0·7 ml min−1 kg−1, mean ± se) in patients with liver disease (69–88%, group means) as were unconjugated cholic acid (51–68%) and glycocholic acid (66–83%) clearance. 3. Extensive regurgitation of labelled conjugated cholic acid (after unconjugated cholic acid tracer injection) among cholestatic patients accounted for 69 ± 5% of total 14C remaining in serum at 70 min, thus masking a less-impaired uptake process. 4. The hepatic extraction efficiency for conjugated cholic acid among controls (86 ± 8%) was greater than that for unconjugated cholic acid (60 ± 4%), and was greatly reduced among patients (7–27%, group means). 5. Normal subjects and patients with cirrhosis without cholestasis did not distribute the isotope to extravascular, extrahepatic spaces, in contrast to cholestatic patients with serum bile acid concentration > 149μmol/l. 6. Careful evaluation of serum disappearance of bile acids as well as chromatographic separation of regurgitated metabolites, could provide investigators with indirect evidence of defects in the rate-limiting steps (uptake, conjugation or excretion) of hepatic bile acid transport.

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