Enhancement of the Urinary Excretion of Non-Sulphated and Sulphated Radioactive Bile Acids by Sodium Acetate in the Bile Duct Obstructed Rat

1985 ◽  
Vol 68 (1) ◽  
pp. 63-70 ◽  
Author(s):  
A. Chitranukroh ◽  
G. Taggart ◽  
B. H. Billing
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Urinary Excretion ◽  
Glomerular Filtration ◽  
Bile Acids ◽  
Renal Clearance ◽  
Sodium Acetate ◽  
Pharmacological Agents ◽  
Renal Clearances ◽  
Inhibition Studies

1. The renal clearances of [14C]glycocholate, [14C]taurocholate and [3H]glycochenodeoxycholate-3-sulphate were determined in bile duct obstructed rats. 2. Comparisons of the bile acid clearances with glomerular filtration rates (GFR) indicate that most of the filtered bile acids are reabsorbed. 3. Inhibition studies with p-aminohippurate (PAH) and probenecid suggest that a proportion of the bile acids in urine is secreted. 4. Attempts were made to increase the renal clearance of the bile acids by the administration of pharmacological agents. 5. An infusion of sodium acetate (0.3 mol/l) increased the clearance of the radioactive bile acids and augmented the urinary excretion of endogenous 3α-hydroxy bile acids and reduced their concentration in plasma.

scholarly journals Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats

1991 ◽  
Vol 280 (2) ◽  
pp. 373-377 ◽  
Author(s):  
S Dueland ◽  
J Reichen ◽  
G T Everson ◽  
R A Davis
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Liver Function ◽  
Urinary Excretion ◽  
Bile Acids ◽  
Bile Duct Ligation ◽  
Microsomal Cytochrome ◽  
Duct Ligation ◽  
Cytochrome P 450

We examined how total blockage of biliary excretion, the major pathway through which cholesterol and bile acids are removed from the body, affects liver function, cholesterol and bile acid metabolism and homoeostasis. After 4 weeks of bile-duct ligation, rats showed impaired liver function, as documented by elevations in serum bilirubin and alkaline phosphatase activity. Moreover, bile-duct ligation decreased by about 30% both the amount of microsomal cytochrome P-450 in the liver and the elimination of aminopyrine in vivo, a reliable index in vivo of microsomal mixed-function oxidase activity. Cholesterol and bile acid contents in livers of bile-duct-ligated rats were doubled compared with sham-operated controls. Despite the increase in the contents of cholesterol and bile acids in liver, activities of the respective rate-limiting enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, were doubled. Serum concentrations of bile acids and free cholesterol increased 25- and 4-fold respectively. The large increase in serum bile acids was associated with a 380-fold increase in the urinary excretion of bile acids. Although there is a general decrease in cytochrome P-450 content and drug metabolism involving cytochrome P-450-containing hydroxylases, the activity of cholesterol 7 alpha-hydroxylase, also a cytochrome P-450-containing enzyme, is actually increased. These data show that complete obstruction of the bile duct results in the selective impairment of microsomal cytochrome P-450. Increased activity of 7 alpha-hydroxylase, bile acid synthesis and urinary excretion provides an alternative excretory pathway that helps to maintain cholesterol homoeostasis when the biliary excretory pathway is eliminated.

Evidence for Renal Control of Urinary Excretion of Bile Acids and Bile Acid Sulphates in the Cholestatic Syndrome

1977 ◽  
Vol 52 (1) ◽  
pp. 51-65 ◽  
Author(s):  
J. A. Summerfield ◽  
Julia Cullen ◽  
S. Barnes ◽  
Barbara H. Billing
Keyword(s):  
Liquid Chromatography ◽  
Bile Acid ◽  
Urinary Excretion ◽  
Bile Acids ◽  
Renal Clearance ◽  
Acid Output ◽  
Total Bile Acid ◽  
Gas Liquid Chromatography ◽  
Acid Sulphate ◽  
Total Bile Acids

1. The bile acids and bile acid sulphates in the urine, serum and bile of eight cholestatic patients were studied quantitatively by gas-liquid chromatography and gas-liquid chromatography/mass spectrometry. 2. The primary bile acids (cholic acid and chenodeoxycholic acid) comprised on average 94% of the total bile acids in bile, 70% in the serum and 64% in urine. 3. The percentage composition of bile acids in bile was relatively constant and was not influenced by the degree of cholestasis. In contrast, in the serum only the primary bile acids were increased, the concentrations of the secondary bile acids (deoxycholic acid and lithocholic acid) and the minor bile acids remaining constant. 4. The data do not support the hypothesis that monohydroxy bile acids accumulate in cholestasis and are related to the pathogenesis of this syndrome. 5. The pattern of bile acid urinary excretion was similar to that in the serum. But in one patient, 3α,7β,12α-trihydroxy-5β-cholan-24-oic acid was a principal urinary bile acid, although very low concentrations of the compound were found in that patient's serum, suggesting that some of the minor bile acids in urine may originate by epimerization in the kidney. 6. In bile only a small proportion of the bile acids was sulphated (range 2·1–4·6%) and in serum the degree of sulphation was very variable (9–50%). However, in urine, sulphate esters accounted for a large proportion of the total bile acids (33–72%). 7. The output of bile acid sulphate in the urine was related to the urine total bile acid output but the serum concentration of bile acid sulphate remained relatively constant. Consequently, in contrast to the non-sulphated bile acids, whose renal clearance was relatively constant, the renal clearance of sulphated bile acids was directly related to the urine total bile acid output. This finding is inconsistent with the earlier hypothesis that their predominance in urine was due to a high renal clearance. It may indicate renal synthesis of some of the bile acid sulphates in the urine and/or inhibition of active renal tubular reabsorption of sulphated bile acids by non-sulphated bile acids.

scholarly journals Bile acid diarrhoea: from diagnosis to treatment

2020 ◽  
Vol 18 (5) ◽  
pp. 36-41
Author(s):  
V.P. Novikova ◽  
◽  
L.N. Belousova ◽  
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Bile Acids ◽  
Enterohepatic Circulation ◽  
Diet Therapy ◽  
Diagnostic Methods ◽  
Chronic Diarrhoea ◽  
Common Cause ◽  
Diagnosis And Management

Bile acid diarrhoea is a common cause of chronic diarrhoea associated with disturbance of the enterohepatic circulation: either excessive biosynthesis/secretion of bile acids or disordered absorption of bile acids in the ileum. At the same time bile acid diarrhoea is an insufficiently studied, frequently underestimated condition, and the questions remain concerning its diagnosis and management. The work discusses the main groups of causes of this pathology, modern diagnostic methods and the difficulties of a differential search. Also, the article offers information about the diet therapy of bile duct diarrhoea and the main groups of administered medications, in particular, modern enterosorbents.

Bile duct cells: a novel in vitro model for the study of lipid metabolism and bile acid production

1999 ◽  
Vol 276 (2) ◽  
pp. G407-G414 ◽  
Author(s):  
Monika Zoltowska ◽  
Edgard E. Delvin ◽  
Khazal Paradis ◽  
Ernest Seidman ◽  
Emile Levy
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Bile Acids ◽  
Cytokeratin 19 ◽  
Sterol Metabolism ◽  
Hmg Coa Reductase ◽  
Biliary Epithelium ◽  
Duct Cells ◽  
Coa Reductase

Immortalized bile duct cells (BDC), derived from transgenic mice harboring the SV40 thermosensitive immortalizing mutant gene ts458, were utilized to investigate the role of the biliary epithelium in lipid and sterol metabolism. This cell model closely resembles the in vivo situation because it expresses the specific phenotypic marker cytokeratin 19 (CK-19), exhibits the formation of bile duct-like structures, and displays well-formed microvilli projected from the apical side to central lumen. The BDC were found to incorporate [14C]oleic acid (in nmol/mg protein) into triglycerides (121 ± 6), phospholipids (PL; 59 ± 3), and cholesteryl ester (16 ± 1). The medium lipid content represented 5.90 ± 0.16% ( P < 0.005) of the total intracellular production, indicating a limited lipid export capacity. Analysis of PL composition demonstrated the synthesis of all classes of polar lipids, with phosphatidylcholine and phosphatidylethanolamine accounting for 60 ± 1 and 24 ± 1%, respectively, of the total. Differences in PL distribution were apparent between cells and media. Substantial cholesterol synthesis was observed in BDC, as determined by the incorporation of [14C]acetate suggesting the presence of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway. With the use of [14C]acetate and [14C]cholesterol as precursors, both tauro- and glycoconjugates of bile acids were synthesized, indicating the presence of cholesterol 7α- and 26R-hydroxylases, the key enzymes involved in bile acid formation. The transport of bile acids was not limited, as shown by their marked accumulation in the medium (>6-fold of cell content). HMG-CoA reductase (53.0 ± 6.7), cholesterol 7α-hydroxylase (15.5 ± 0.5), and acyl-CoA:cholesterol acyltransferase (ACAT; 201.7 ± 10.2) activities (in pmol ⋅ min−1 ⋅ mg protein−1) were present in the microsomal fractions. Our data show that biliary epithelial cells actively synthesize lipids and may directly contribute bile acids to the biliary fluid in vivo. This BDC line thus represents an efficient experimental tool to evaluate biliary epithelium sterol metabolism and to study biliary physiology.

Urinary excretion of bile acids in bile duct-ligated rats

2003 ◽  
Vol 38 (6) ◽  
pp. 561-566 ◽  
Author(s):  
Yukiko Takada ◽  
Naoyo Sano ◽  
Hajime Takikawa
Keyword(s):  
Bile Duct ◽  
Urinary Excretion ◽  
Bile Acids

Permeation patterns of polar nonelectrolytes across the guinea pig biliary tree

1984 ◽  
Vol 247 (5) ◽  
pp. G527-G536 ◽  
Author(s):  
N. Tavoloni
Keyword(s):  
Steady State ◽  
Bile Acid ◽  
Bile Duct ◽  
Guinea Pig ◽  
Bile Acids ◽  
Bile Flow ◽  
Biliary Tree ◽  
Canalicular Membrane ◽  
Biliary Clearance ◽  
Spontaneous Secretion

The biliary permeation of polar nonelectrolytes was studied in anesthetized, bile duct-cannulated guinea pigs with functional cholecystectomy and nephrectomy. During spontaneous secretion, the steady-state bile-to-plasma ratio (B/P) of [14C]urea, [14C]erythritol, [14C]mannitol, [3H]sucrose, and [3H]inulin was 1.02, 0.90, 0.38, 0.12, and 0.04, respectively. Differently structured hydroxy bile acids, but not taurodehydrocholate, reversibly diminished [14C]erythritol and [14C]mannitol B/P during choleresis, and with some of them, particularly taurocholate and glycochenodeoxycholate, the biliary clearance of either solute declined below precholeretic levels. For any given hydroxy bile acid, the degree of B/P diminution was directly related to the molecular radii of these two inert carbohydrates. All bile acids failed to decrease [14C]urea, [3H]sucrose, and [3H]inulin B/P. On the contrary, most of them irreversibly increased [3H]sucrose and [3H]inulin permeability. These results suggest that in the guinea pig 1) hydroxy bile acids diminish the size or rearrange the architecture of the canalicular membrane "aqueous pores" through which [14C]erythritol and [14C]mannitol enter the canaliculus, and 2) solutes of the size of or smaller than [14C]mannitol enter bile primarily through a transcellular route, whereas [3H]sucrose, and [3H]inulin permeate mainly via a transjunctional shunt pathway. These studies indicate that [14C]erythritol and [14C]mannitol cannot be used to estimate canalicular bile flow in this species.

scholarly journals Neither intestinal sequestration of bile acids nor common bile duct ligation modulate the expression and function of the rat ileal bile acid transporter

Hepatology ◽  
1998 ◽  
Vol 28 (4) ◽  
pp. 1081-1087 ◽  
Author(s):  
Marco Arrese ◽  
Michael Trauner ◽  
Robert J. Sacchiero ◽  
Michael W. Crossman ◽  
Benjamin L. Shneider
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Common Bile Duct ◽  
Bile Acids ◽  
Bile Duct Ligation ◽  
Common Bile Duct Ligation ◽  
Duct Ligation ◽  
Bile Acid Transporter ◽  
Acid Transporter ◽  
And Function

Induction of short heterodimer partner 1 precedes downregulation of Ntcp in bile duct-ligated mice

2002 ◽  
Vol 282 (1) ◽  
pp. G184-G191 ◽  
Author(s):  
Gernot Zollner ◽  
Peter Fickert ◽  
Dagmar Silbert ◽  
Andrea Fuchsbichler ◽  
Conny Stumptner ◽  
...  
Keyword(s):  
Steady State ◽  
Bile Acid ◽  
Bile Duct ◽  
Protein Expression ◽  
Mrna Expression ◽  
Bile Acids ◽  
Serum Bile Acid ◽  
Acid Uptake ◽  
Mrna Levels ◽  
Short Heterodimer Partner

Cholestasis is associated with retention of bile acids and reduced expression of the Na+/taurocholate cotransporter (Ntcp), the major hepatocellular bile acid uptake system. This study aimed to determine whether downregulation of Ntcp in obstructive cholestasis 1) is a consequence of bile acid retention and 2) is mediated by induction of the transcriptional repressor short heterodimer partner 1 (SHP-1). To study the time course for the changes in serum bile acid levels as well as SHP-1 and Ntcp steady-state mRNA levels, mice were subjected to common bile duct ligation (CBDL) for 3, 6, 12, 24, 72, and 168 h and compared with sham-operated controls. Serum bile acid levels were determined by radioimmunoassay. SHP-1 and Ntcp steady-state mRNA expression were assessed by Northern blotting. In addition, Ntcp protein expression was studied by Western blotting and immunofluorescence microscopy. Increased SHP-1 mRNA expression paralleled elevations of serum bile acid levels and was followed by downregulation of Ntcp mRNA and protein expression in CBDL mice. Maximal SHP-1 mRNA expression reached a plateau phase after 6-h CBDL (12-fold; P < 0.001) and preceded the nadir of Ntcp mRNA levels (12%, P < 0.001) by 6 h. In conclusion, bile acid-induced expression of SHP-1 may, at least in part, mediate downregulation of Ntcp in CBDL mice. These findings support the concept that downregulation of Ntcp in cholestasis limits intracytoplasmatic accumulation of potentially toxic bile acids.

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