Influence of Deoxycholic Acid on Biliary Lipids in Man

1977 ◽  
Vol 53 (3) ◽  
pp. 249-256 ◽  
Author(s):  
J. Ahlberg ◽  
B. Angelin ◽  
K. Einarsson ◽  
K. Hellström ◽  
B. Leijd

1. The duodenal bile acid composition was analysed in 24 control subjects and 107 patients with various types of hyperlipoproteinaemia. A highly significant negative correlation was observed between the proportions of deoxycholic acid and cholic acid as well as between deoxycholic acid and chenodeoxycholic acid. Patients with gall-bladder disease had an increased proportion of deoxycholic acid in their bile. 2. Eight control subjects were studied before and during the ingestion of 1·9 mmol (0·75 g) of deoxycholic acid daily. In these subjects a rise in the proportion of deoxycholic acid was also accompanied by a fall in the proportion of both cholic acid and chenodeoxycholic acid in duodenal bile. 3. The biliary lipid composition and cholesterol saturation was determined before and during the administration of 1·9 mmol (0·75 g) of chenodeoxycholic acid (n = 12) or deoxycholic acid (n = 8) daily for 3–4 weeks. The cholesterol saturation was decreased during the chenodeoxycholic acid ingestion whereas no change occurred in bile saturation during deoxycholic acid administration. 4. Ingestion of chenodeoxycholic acid lowered serum triglyceride and deoxycholic acid lowered the serum cholesterol.

1979 ◽  
Vol 25 (2) ◽  
pp. 264-268 ◽  
Author(s):  
O Mäentausta ◽  
O Jänne

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.


1976 ◽  
Vol 155 (2) ◽  
pp. 401-404 ◽  
Author(s):  
E S. Haslewood ◽  
G A. D. Haslewood

1. The 3-sulphates of cholic, chenodeoxycholic and deoxycholic acids were prepared as crystalline disodium salts. 2. The method described shows that it is possible to prepare specific sulphate esters of polyhydroxy bile acids and to remove protecting acyl groups without removing the sulphate. 3. A study of bile acid sulphate solvolysis showed that none of the usual methods give the original bile acid in major yield in a single step. 4. An understanding of the preparation, properties and methods of solvolysis of bile acid sulphates is basic for investigations of cholestasis and liver disease.


1974 ◽  
Vol 47 (5) ◽  
pp. 425-433
Author(s):  
K. Einarsson ◽  
K. Hellström ◽  
M. Kallner

1. The turnover of [24−14C]cholic acid and [3H]chenodeoxycholic acid and the faecal excretion of neutral steroids were studied in six normolipaemic subjects before and during the ingestion of 1.3–2.6 mmol (0.5–1.0 g) of deoxycholic acid/day. Before the second study the subjects had been fed deoxycholic acid for 2 weeks. 2. The administration of deoxycholic acid did not appear to influence cholesterol metabolism as judged by the absence of change in the serum concentrations and the overall transformation into primary bile acids and neutral faecal steroids. 3. During the deoxycholic acid feeding period the mean total synthesis of bile acids was reduced by about 30%, corresponding to approximately 0.25 mmol (100 mg)/day. In one subject the pool size and in another the synthesis of cholic acid remained unchanged; otherwise the cholic acid pool size and its rate of formation decreased in all subjects. No consistent effects were observed with regard to the turnover of chenodeoxycholic acid. 4. Assuming that the bile acid turnover is equivalent to bile acid excretion then the total amount of cholesterol eliminated as bile acids and neutral faecal steroids averaged between 1.6 and 1.8 mmol/day before and during the administration of deoxycholic acid.


2019 ◽  
Vol 151 (6) ◽  
pp. 820-833 ◽  
Author(s):  
Alexandr V. Ilyaskin ◽  
Florian Sure ◽  
Viatcheslav Nesterov ◽  
Silke Haerteis ◽  
Christoph Korbmacher

We recently demonstrated that bile acids, especially tauro-deoxycholic acid (t-DCA), modify the function of the acid-sensing ion channel ASIC1a and other members of the epithelial sodium channel (ENaC)/degenerin (DEG) ion channel family. Surprisingly, ASIC1 shares a high degree of structural similarity with the purinergic receptor P2X4, a nonselective cation channel transiently activated by ATP. P2X4 is abundantly expressed in the apical membrane of bile duct epithelial cells and is therefore exposed to bile acids under physiological conditions. Here, we hypothesize that P2X4 may also be modulated by bile acids and investigate whether t-DCA and other common bile acids affect human P2X4 heterologously expressed in Xenopus laevis oocytes. We find that application of either t-DCA or unconjugated deoxycholic acid (DCA; 250 µM) causes a strong reduction (∼70%) of ATP-activated P2X4-mediated whole-cell currents. The inhibitory effect of 250 µM tauro-chenodeoxycholic acid is less pronounced (∼30%), and 250 µM chenodeoxycholic acid, cholic acid, or tauro-cholic acid did not significantly alter P2X4-mediated currents. t-DCA inhibits P2X4 in a concentration-dependent manner by reducing the efficacy of ATP without significantly changing its affinity. Single-channel patch-clamp recordings provide evidence that t-DCA inhibits P2X4 by stabilizing the channel’s closed state. Using site-directed mutagenesis, we identifiy several amino acid residues within the transmembrane domains of P2X4 that are critically involved in mediating the inhibitory effect of t-DCA on P2X4. Importantly, a W46A mutation converts the inhibitory effect of t-DCA into a stimulatory effect. We conclude that t-DCA directly interacts with P2X4 and decreases ATP-activated P2X4 currents by stabilizing the closed conformation of the channel.


1974 ◽  
Vol 46 (2) ◽  
pp. 183-190
Author(s):  
Kurt Einarsson ◽  
Kjell Hellström

1. The turnover of deoxycholic acid and chenodeoxycholic acid was studied in six normolipaemic patients after oral administration of trace amounts of isotopically labelled compounds. 2. The mean values for half-life, pool size and turnover of deoxycholic acid were 3·0 days, 663 mg and 171 mg/day respectively. The corresponding values recorded for chenodeoxycholic acid were 2·8 days, 781 mg and 207 mg/day. 3. A comparison of the turnover rates of deoxycholic acid and cholic acid in three subjects indicated that 25–61% of the cholic acid was converted into deoxycholic acid. 4. Only trace amounts of radioactivity were recovered in the trihydroxycholanic acid fraction of duodenal bile after the administration of [14C]deoxycholic acid or [3H]chenodeoxycholic acid.


1992 ◽  
Vol 61 (2-3) ◽  
pp. 291-304 ◽  
Author(s):  
N.M. Delzenne ◽  
P.Buc Calderon ◽  
H.S. Taper ◽  
M.B. Roberfroid

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