Bile Flow and Composition During Bile Acid Depletion and Administration

1974 ◽  
Vol 52 (2) ◽  
pp. 334-348 ◽  
Author(s):  
Curtis D. Klaassen

Relatively similar concentrations of the inorganic ions were detected in rat, rabbit, and dog bile; however, dog bile had a higher concentration of protein, cholesterol, phospholipid phosphorous, and percentage solids than rat bile, and rabbit bile had the lowest concentration. The biliary excretion of bile acids was altered in each species by: (1) interruption of the enterohepatic circulation; (2) rapid administration of an exogenous load of bile acids; and (3) constant infusion of an exogenous load of bile acids. Bile acid and phospholipid phosphorous concentration and percentage solids increased after bile acid administration in all three species; however, species differences in bilirubin concentration were observed and a marked decrease was detected in rabbit and dog bile but it markedly increased in rat bile. When the enterohepatic circulation was interrupted in the dog and rat, the bile acid concentration markedly decreased with only minor changes in bile flow. This not only supports the theory that there is a bile salt independent fraction of bile formation, but also demonstrates that canalicular bile formation can be maintained at relatively normal rates with almost no excretion of bile acids. Marked discrepancy between bile acid excretion and bile flow was observed in the rat after bile acid administration, in that a marked increase in bile acid excretion was observed but little or no increase in flow. When bile flow was plotted against bile acid excretion for the three species, the slope of the line was less during bile acid administration than during depletion, indicating that the bile acids are accompanied by less water during bile acid administration than during depletion. Variation in the bile flow intercept with zero bile acid excretion (thought to represent the bile salt-independent fraction) was relatively large, which is probably due in part to alteration in the production of the bile salt independent fraction when bile acid secretion is altered. It appears that both the choleretic property of bile acids varies during various rates of bile acid excretion and the bile salt-independent fraction is not constant. Therefore, calculation of the bile salt independent fraction as previously performed should be interpreted with extreme caution. Thus, it appears difficult to determine the quantitative importance of bile acid excretion in bile formation.

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 317-318
Author(s):  
Renan Antunes Donadelli ◽  
Julia G Pezzali ◽  
Patrícia M Oba ◽  
Kelly S Swanson ◽  
Craig N Coon ◽  
...  

Abstract In 2018 the Food and Drug Administration (FDA) released a statement that grain-free diets may be related to the increased incidence of dilated cardiomyopathy (DCM) in dogs. This statement was made despite all implicated diets meeting nutrient requirements published by the Association of American Feed Controls Official (AAFCO) and enforced by State Officials. Many of these dogs presented with low plasma or whole blood taurine concentrations, and as such, we hypothesized that feeding these diets would result in reduced taurine status over a 26 wk feeding period. The objective of this study was to determine the effects of feeding a grain-free diet to large breed dogs on taurine status and overall health. Eight Labrador Retrievers (4 males, 4 females; Four Rivers Kennel, MO) were individually housed and fed a commercial complete and balanced grain-free diet (Acana Pork and Squash formula; APS; moisture 8.40%, crude protein 37.81%, crude fat 18.78%, ash 8.06%, and total dietary fiber 11.40%) for 26 weeks. Fasted blood samples were collected at week 0 and 26 for analyses of plasma and whole blood taurine. Urine was collected by free catch and analyzed for taurine and creatinine. Fresh fecal samples were collected and analyzed for bile acids. Data were analyzed using the GLIMMIX procedure with repeated measures in SAS (v. 9.4). Dogs were healthy throughout the duration of the trial. Urinary taurine to creatinine ratio did not change throughout the feeding period (wk 0 = 0.25 vs. wk 26 = 0.28). Fecal bile acid excretion increased after 26 weeks of feeding APS to dogs. Despite the higher fecal excretion of bile acids, plasma and whole blood taurine increased over the 26 wk feeding period. In conclusion, feeding APS for 26 wk results in increased taurine status in large breed dogs, despite higher excretion of fecal bile acids.


1996 ◽  
Vol 90 (4) ◽  
pp. 315-319 ◽  
Author(s):  
M. A. Färkkilä ◽  
K. J. Kairemo ◽  
M. J. Taavitsainen ◽  
T. A. Strandberg ◽  
T. A. Miettinen

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids<10 mg day−1 kg−1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day−1 kg−1, n = 13). 3. Faecal bile acid excretion was 5.9 ± 1.0 mg day−1 kg−1 in control subjects and 45.7 ± 6.1 mg day−1 kg−1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T½) was 95.6 ± 16.3 h and 14.1 ± 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 ± 84 μg/ml compared with 400 ± 59 μg/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P<0.001), with 75SeHCAT T½ (r = −0.524, P<0.05) and with Schilling test (r = −0.591, P<0.05). Significant correlations were also obtained for Δ8-cholestenol with faecal bile acids (r = 0.784, P<0.001) and 75SeHCAT (r = −0.505, P<0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = −0.702, P<0.01). Using mean + 2 SD of lathosterol (In μg/ml cholesterol) as a cut-off value and 10 mg day−1 kg−1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.


1996 ◽  
Vol 52 (3) ◽  
pp. 489-495
Author(s):  
Makoto Hoshino ◽  
Akitaka Tanaka ◽  
Tomihiro Hayakawa ◽  
Takayuki Ohiwa ◽  
Kenji Katagiri ◽  
...  

1968 ◽  
Vol 47 (5) ◽  
pp. 1002-1014 ◽  
Author(s):  
Norman B. Javitt ◽  
Sidney Emerman

1974 ◽  
Vol 52 (3) ◽  
pp. 389-403 ◽  
Author(s):  
Carl A. Goresky ◽  
Henry H. Haddad ◽  
Warren S. Kluger ◽  
Brita E. Nadeau ◽  
Glen G. Bach

Of the processes involved in the handling of a bilirubin load, the biliary secretory maximum or Tm for bilirubin has been regarded as rate limiting, and as a characteristic of liver function. In the present study, bile flow was varied by use of bile acid infusions, in order to determine whether the Tm is indeed constant or whether it varies with flow. Anesthetized dogs, with bile flow stabilized by cholinergic blockade, were studied during taurocholate infusions. In these animals the ductular component of flow is relatively inhibited and the bile flow rate increases approximately in proportion to the rate of excretion of taurocholate. The maximal biliary excretion rate of bilirubin was found to increase linearly with flow and taurocholate excretion, in a significant fashion, but, in contrast to the relation between taurocholate excretion and flow, a significantly large intercept remained on linear extrapolation towards zero flow. The basis for the large intercept is a great increase in the bilirubin concentration in bile as the flow is decreased. This results in a simultaneous sharp increase in the molar ratio (bilirubin/taurocholate) at very low flow rates.We have inferred, on the basis of the preceding data, that the capacity for bilirubin transport is linked to the secretion of bile acids into bile. At low rates of supply of bile acids, little of the material will reach the centers of the hepatic lobules, and the contribution of bile acids to bile flow at that site will be relatively low. At higher rates of bile acid infusion or supply, increased amounts of the bile acids will reach the centers of the lobules and contribute to increased bile formation in these areas. It appears that this is the mechanism which underlies the change in the transport maximum for bilirubin with change in the rate of bile salt excretion.


1992 ◽  
Vol 262 (5) ◽  
pp. G806-G812 ◽  
Author(s):  
R. Bruck ◽  
P. Haddad ◽  
J. Graf ◽  
J. L. Boyer

To study the effect of volume regulation on bile secretory function, isolated perfused rat livers (IPRL) were exposed to hypotonic stress (45 mM NaCl) while bile flow and the biliary excretion of bile acids and horseradish peroxidase (HRP) were assessed. Hypotonic stress induced a biphasic increase in bile flow, which rose in the first minute from 1.1 +/- 0.2 to 1.7 +/- 0.1 microliter.min-1.g liver-1 (P less than 0.01), an effect attributed to rapid osmotic equilibration of water, then increased further between 3 and 5 min to 1.6 +/- 0.1 microliter.min-1.g liver-1 (P less than 0.01, followed by a subsequent return to baseline. HRP excretion in bile increased during the second peak of bile flow from 0.9 +/- 0.2 to 1.1 +/- 0.2 ng.min-1.g liver-1, P less than 0.01. Pretreatment with colchicine but not lumicolchicine completely abolished the latter increase in bile flow and HRP excretion as did BaCl2 (1 mM), an inhibitor of both K+ channels and regulatory volume decrease (RVD) in hepatocytes. When sodium taurocholate was infused (1 mumol/min), hypotonic stress induced an even larger increase in the second peak of bile flow (5.1 +/- 0.7 microliters/g liver, P less than 0.01) and higher rates of bile acid excretion than in control perfusions with bile acid (126.2 +/- 21.0 vs. 99.0 +/- 17.1 nmol.min-1.g liver-1, P less than 0.05). These data suggest that both bile flow and bile acid excretion are stimulated during RVD by mechanisms that involve both K+ channels and microtubule-dependent exocytosis at the canalicular (apical) membrane domain.


1962 ◽  
Vol 203 (6) ◽  
pp. 1029-1032 ◽  
Author(s):  
Jean D. Wilson

The influence of dietary cholesterol on fecal excretion of bile acids has been studied in rats fed isocaloric quantities of purified diets that varied only in cholesterol content. Addition of dietary cholesterol clearly resulted in an increase in excretion of total bile acids, as well as in conversion of cholesterol-4-C14 to bile acid-C14. An acceleration in bile acid excretion as a result of cholesterol feeding was demonstrated to be independent of dietary cholic acid and to occur despite suppression of the bowel flora. These results suggest that not only does absorbed dietary cholesterol play a role in determining the rate of bile acid formation but that the adaptation of bile acid synthesis to cholesterol feeding may in part be a determining factor in the varying response of different species to cholesterol feeding.


2003 ◽  
Vol 17 (4) ◽  
pp. 265-271 ◽  
Author(s):  
Richard N Redinger

The coordinated effect of lipid activated nuclear hormone receptors; liver X receptor (LXR), bound by oxysterol ligands and farnesoid X receptor (FXR), bound by bile acid ligands, act as genetic transcription factors to cause feed-forward cholesterol catabolism to bile acids and feedback repression of bile acid synthesis, respectively. It is the coordinated action of LXR and FXR, each dimerized to retinoid X receptor, that signal nuclear DNA response elements to encode proteins that prevent excessive cholesterol accumulation and bile salt toxicity, respectively. LXR helps prevent hypercholesterolemia by enhancing transporters for cholesterol efflux that enhance reverse cholesterol transport, while FXR enhances intestinal reabsorption and preservation of bile salts by increasing the ileal bile acid binding protein. FXR also targets sodium taurocholate cotransport peptide and bile salt export pump (protein) genes to limit bile salt uptake and enhance export, respectively, which prevents bile salt toxicity. Other nuclear hormone receptors such as pregnan X receptor, which share the obligate partner, retinoid X receptor, and vitamin D receptor also function as bile acid sensors to signal detoxification by hydroxylation of toxic bile acids. Pharmacologically targeted receptor agonists (or antagonists) may be developed that alter cholesterol and bile salt concentrations by modulating nuclear hormone receptors and/or their coactivators or corepressors to positively affect cholesterol homeostasis and bile salt metabolism. It is the coordinated transcription factor action of LXR, which responds to ligand binding of circulating oxysterols in both liver and peripheral tissues, and FXR responding to bile salts within the enterohepatic circulation that make possible the regulation of cholesterol and bile acid homeostasis.


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