scholarly journals Microtubule-independent choleresis and anti-cholestatic action of tauroursodeoxycholate in colchicine-treated rat liver

1992 ◽  
Vol 288 (2) ◽  
pp. 613-617 ◽  
Author(s):  
T Nakai ◽  
K Katagiri ◽  
M Hoshino ◽  
T Hayakawa ◽  
T Ohiwa
Keyword(s):  
Bile Salt ◽  
Ursodeoxycholic Acid ◽  
Bile Flow ◽  
Bile Salts ◽  
Intracellular Transport ◽  
Taurocholic Acid ◽  
Slight Improvement ◽  
Pre Treatment ◽  
Excretion Rates ◽  
Rat Livers

In order to cast light on the anti-cholestatic and cytoprotective properties of ursodeoxycholic acid (UDCA), intrahepatic transport and secretion of bile salts and biliary phospholipids were investigated by using isolated perfused livers from colchicine-pretreated rats. Administration of taurocholic acid (TCA) after colchicine pretreatment induced marked cholestasis. Tauroursodeoxycholic acid (TUDCA) treatment, in contrast, was associated with maintenance of bile flow, with excretion rates of bile acids and phospholipids similar to those in control animals. Furthermore, TCA-induced cholestasis in colchicine-treated rat livers was clearly decreased by co-administration of TUDCA. Although simultaneous addition of UDCA also showed slight improvement, with or without taurine pre-treatment, biliary bile-salt analysis also showed that cholestasis was markedly remitted as the excretion of taurine-conjugated UDCA was increased. The results suggest that the cytoprotective and anti-cholestatic effects of TUDCA may be linked to action at the intrahepatocyte level, represented by mild detergent effects on organelle lipids and preservation of intracellular transport even under microtubule-dysfunctional conditions. In addition, it was indicated that cytoprotective effects of UDCA may also be exerted after its conjugation with taurine inside hepatocytes.

scholarly journals Effect of taurochenodeoxycholate or tauroursodeoxycholate upon biliary output of phospholipids and plasma-membrane enzymes, and the extent of cell damage, in isolated perfused rat livers

1983 ◽  
Vol 216 (1) ◽  
pp. 107-111 ◽  
Author(s):  
S G Barnwell ◽  
P J Lowe ◽  
R Coleman
Keyword(s):  
Plasma Membrane ◽  
Bile Salt ◽  
Bile Flow ◽  
Bile Salts ◽  
Cell Damage ◽  
Characteristic Difference ◽  
Membrane Enzymes ◽  
Hepatobiliary System ◽  
Rat Livers

Isolated perfused rat livers were used to study the effects of taurochenodeoxycholate (TCDC) and tauroursodeoxycholate (TUDC) upon some aspects of biliary composition. After depletion of the endogenous bile salt pool of the liver, introduction of either bile salt brought about increases in bile flow, bile salt output and biliary phospholipid output. Taurochenodeoxycholate needed a lower biliary concentration to produce phospholipid output than did tauroursodeoxycholate. TCDC perfusion caused a substantial output of plasma-membrane enzymes (5′-nucleotidase and alkaline phosphodiesterase) into the bile, whereas TUDC caused little output of either enzyme; this may represent a characteristic difference between the effects of the two bile salts on the hepatobiliary system. The results from TUDC perfusion indicate also that much of the output of biliary phospholipid promoted by bile salts, may be independent of the output of plasma-membrane enzymes promoted by bile salts.

Effects of essential fatty acid deficiency on enterohepatic circulation of bile salts in mice

2009 ◽  
Vol 297 (3) ◽  
pp. G520-G531 ◽  
Author(s):  
S. Lukovac ◽  
E. L. Los ◽  
F. Stellaard ◽  
E. H. H. M. Rings ◽  
H. J. Verkade
Keyword(s):  
Fatty Acid ◽  
Bile Salt ◽  
Mrna Expression ◽  
Essential Fatty Acid ◽  
Bile Flow ◽  
Bile Salts ◽  
Enterohepatic Circulation ◽  
Synthesis Rate ◽  
Bile Production ◽  
Deficient Mice

Essential fatty acid (EFA) deficiency in mice has been associated with increased bile production, which is mainly determined by the enterohepatic circulation (EHC) of bile salts. To establish the mechanism underlying the increased bile production, we characterized in detail the EHC of bile salts in EFA-deficient mice using stable isotope technique, without interrupting the normal EHC. Farnesoid X receptor (FXR) has been proposed as an important regulator of bile salt synthesis and homeostasis. In Fxr −/− mice we additionally investigated to what extent alterations in bile production during EFA deficiency were FXR dependent. Furthermore, we tested in differentiating Caco-2 cells the effects of EFA deficiency on expression of FXR-target genes relevant for feedback regulation of bile salt synthesis. EFA deficiency-enhanced bile flow and biliary bile salt secretion were associated with elevated bile salt pool size and synthesis rate (+146 and +42%, respectively, P < 0.05), despite increased ileal bile salt reabsorption (+228%, P < 0.05). Cyp7a1 mRNA expression was unaffected in EFA-deficient mice. However, ileal mRNA expression of Fgf15 (inhibitor of bile salt synthesis) was significantly reduced, in agreement with absent inhibition of the hepatic bile salt synthesis. Bile flow and biliary secretion were enhanced to the same extent in EFA-deficient wild-type and Fxr −/− mice, indicating contribution of other factors besides FXR in regulation of EHC during EFA deficiency. In vitro experiments show reduced induction of mRNA expression of relevant genes upon chenodeoxycholic acid and a selective FXR agonist GW4064 stimulation in EFA-deficient Caco-2 cells. In conclusion, our data indicate that EFA deficiency is associated with interrupted negative feedback of bile salt synthesis, possibly because of reduced ileal Fgf15 expression.

scholarly journals Acute effects of cholestatic and choleretic bile salts on vasopressin- and glucagon-induced hepato-biliary calcium fluxes in the perfused rat liver

1992 ◽  
Vol 283 (2) ◽  
pp. 575-581 ◽  
Author(s):  
Y Hamada ◽  
A Karjalainen ◽  
B A Setchell ◽  
J E Millard ◽  
F L Bygrave
Keyword(s):  
Bile Salt ◽  
Rat Liver ◽  
Strong Correlation ◽  
Bile Flow ◽  
Bile Salts ◽  
Perfused Rat Liver ◽  
Acute Effects ◽  
Calcium Fluxes ◽  
Principal Effect

The effects were investigated of the choleretic bile salt glycoursodeoxycholate (G-UDCA) and of the cholestatic bile salt taurochenodeoxycholate (T-CDCA) on changes in perfusate Ca2+, glucose and oxygen and in bile calcium and bile flow induced by the administration of (a) vasopressin, (b) glucagon and (c) glucagon plus vasopressin together to the perfused rat liver [Hamada, Karjalainen, Setchell, Millard & Bygrave (1992) Biochem. J. 281, 387-392]. G-UDCA itself increased the secretion of calcium in the bile several-fold, but its principal effect was to augment each of the above-mentioned metabolic events except glucose and oxygen output; particularly noteworthy was its ability to augment the ‘transients’ in bile calcium and bile flow seen immediately after the administration of vasopressin with or without glucagon. T-CDCA, by contrast, produced opposite effects and attenuated all of the parameters measured, and in particular the transients in bile calcium and bile flow. The data provide evidence of a strong correlation between calcium fluxes occurring on both the sinusoidal and the bile-canalicular membranes and that all are modifiable by glucagon, Ca(2+)-mobilizing hormones and bile salts.

Taurocholate, but not taurodehydrocholate, increases biliary permeability to sucrose

1983 ◽  
Vol 245 (5) ◽  
pp. G651-G655 ◽  
Author(s):  
J. Reichen ◽  
M. Le
Keyword(s):  
Bile Salt ◽  
Bile Flow ◽  
Bile Salts ◽  
Biliary Tree ◽  
Secretory Rate ◽  
Plasma Ratio ◽  
Dose Dependent Fashion ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Salt Secretion

To determine whether bile salts alter the permeability of the biliary tree to inert solutes, we investigated the effects of taurocholate and taurodehydrocholate on [14C]sucrose bile-to-plasma ratio in the situ perfused rat liver. Sucrose bile-to-plasma ratio remained virtually constant over a 3-h period in untreated rats. Infusing increasing amounts of taurocholate produced the anticipated dose-dependent increase in bile flow and bile salt secretion up to a maximal secretory rate of 278 nmol X min-1 X g liver-1. When the secretory rate was exceeded, bile flow decreased by 22%. Even at doses below the maximal secretory rate, sucrose bile-to-plasma ratio increased in a dose-dependent fashion. To determine whether this was due to recruitment of more permeable centrizonal hepatocytes, the effect of equimolar amounts of taurodehydrocholate was determined. This nonmicelle-forming bile salt led to more marked choleresis than taurocholate but did not affect sucrose bile-to-plasma ratio. We conclude that taurocholate, but not taurodehydrocholate, leads to a dose-dependent increase in biliary permeability.

scholarly journals Biliary protein output by isolated perfused rat livers. Effects of bile salts

1983 ◽  
Vol 210 (2) ◽  
pp. 549-557 ◽  
Author(s):  
S G Barnwell ◽  
P P Godfrey ◽  
P J Lowe ◽  
R Coleman
Keyword(s):  
Plasma Membrane ◽  
Bile Salt ◽  
Bile Salts ◽  
Serum Proteins ◽  
Critical Micellar Concentration ◽  
Rapid Decline ◽  
Perfusion Medium ◽  
Rat Serum ◽  
Membrane Enzymes ◽  
Rat Livers

The output of proteins into bile was studied by using isolated perfused rat livers. Replacement of rat blood with defined perfusion media deprived the liver of rat serum proteins (albumin, immunoglobulin A) and resulted in a rapid decline in the amounts of these proteins in bile. When bovine serum albumin was incorporated into the perfusion medium it appeared in bile within 20 min and the amount in the bile was determined by the concentration of the protein in the perfusion medium. The use of a defined perfusion medium also deprived the livers of bile salts and the amounts of these, and of plasma-membrane enzymes [5′-nucleotidase (EC 3.1.3.5) and phosphodiesterase I], in bile declined rapidly. Introduction of micelle-forming bile salts (taurocholate or glycodeoxycholate) to the perfusion medium 80 min after liver isolation markedly increased the output of plasma-membrane enzymes but had no effect on the other proteins. The magnitude of this response was dependent on the bile salt used and its concentration in bile; there was little effect on plasma-membrane enzyme output until the critical micellar concentration of the bile salt had been exceeded in the bile. A bile salt analogue, taurodehydrocholate, which does not form micelles, did not produce the enhanced output of plasma-membrane enzymes. This work supports the view that the output of plasma-membrane enzymes in bile is a consequence of bile salt output and also provides evidence for mechanisms by which serum proteins enter the bile.

Effect of bile salt on phosphatidylcholine composition and secretion of hepatic high-density lipoproteins

1990 ◽  
Vol 259 (2) ◽  
pp. G205-G211 ◽  
Author(s):  
S. J. Robins ◽  
J. M. Fasulo ◽  
G. M. Patton
Keyword(s):  
Bile Salt ◽  
Molecular Species ◽  
Bile Salts ◽  
Low Density Lipoproteins ◽  
High Density ◽  
High Density Lipoproteins ◽  
Absolute Amount ◽  
Very Low Density Lipoproteins ◽  
Rat Livers ◽  
Isolated Rat

Bile salts are necessary for the secretion of phosphatidylcholines (PCs) in bile and result in the selective secretion of highly hydrophilic molecular species of PC that contain a 16:0 acyl group. To determine the effect of bile salt on the secretion of PCs in lipoproteins, isolated rat livers were perfused with and without taurocholate. The PC composition of very-low-density lipoproteins (VLDL), newly synthesized by the liver, precisely mirrored the composition of PCs in the whole liver and was not changed with the administration of taurocholate. In contrast, both the composition of PCs in high-density lipoproteins (HDL) and the absolute amount of newly synthesized HDL were markedly affected by the administration of taurocholate. With taurocholate the PC content of HDL was increased, HDL was enriched, like bile, in 16:0 molecular species of PC, and the amount of HDL that was recovered in the perfusate was 2.5-fold greater than without taurocholate (P less than 0.001). These findings suggest that VLDL and HDL are differently derived from within the liver, that the PCs of HDL and bile originate from the same hepatic pool or by the same mechanism, and that both the secretion of bile and HDL from the liver are susceptible to regulation by bile salt.

The effect of cyclosporine A on bile secretion in dogs

1990 ◽  
Vol 68 (1) ◽  
pp. 136-138 ◽  
Author(s):  
Francis R. Sutherland ◽  
Roy M. Preshaw ◽  
Eldon A. Shaffer
Keyword(s):  
Bile Salt ◽  
Cyclosporine A ◽  
Bile Flow ◽  
Common Duct ◽  
Bile Secretion ◽  
Taurocholic Acid ◽  
Duodenal Fistula ◽  
The Common ◽  
Bile Output ◽  
Oral Doses

Cyclosporine A is reported to cause cholestasis, but the evidence is confounded by anesthesia and surgery used in acute experiments. To better investigate the effect of cyclosporine on the liver, bile output was directly measured in three cholecystectomized dogs by cannulating the common duct through a chronic duodenal fistula. Control studies were done 1 month after surgery. Cyclosporine in oral doses of 5, 15, and 50 mg∙kg−1∙d−1 was then given for consecutive 1-week periods. Twice during each study period, bile output was measured for 5 h in fasted, awake animals: 3 h to establish basal conditions, followed by 2 h of taurocholate infusions at 1 and then 2 μmol∙kg−1∙min−1. Under basal conditions, bile flow rose with each dose of cyclosporine, increasing 63, 127, and 179% above control with cyclosporine 5, 15, and 50 mg∙kg−1∙d−1 respectively. Bile flow increased similarly during taurocholic acid stimulation. Cyclosporine had no effect on bile salt or bilirubin secretion. In this chronic dog model isolated from other causes of cholestasis, cyclosporine did not induce cholestasis but rather caused a dose-related choleresis without any change in bile salt secretion.Key words: cyclosporine A, bile, cholestasis, hepatotoxicity.

Effect of Lysine Acetylsalicylate on Biliary Lipid Secretion in Dogs

1975 ◽  
Vol 49 (3) ◽  
pp. 253-256 ◽  
Author(s):  
S. Erlinger ◽  
Dominique Bienfait ◽  
Renee Poupon ◽  
Micheline Dumont ◽  
M. Duval
Keyword(s):  
Bile Salt ◽  
Bile Flow ◽  
Bile Salts ◽  
Biliary Lipid ◽  
Cholesterol Gallstones ◽  
Cholesterol Saturation ◽  
Parallel Increase ◽  
Lysine Acetylsalicylate ◽  
Cholesterol Secretion ◽  
Salt Secretion

1. The influence of lysine acetylsalicylate on bile flow, erythritol clearance and bile salt, phospholipid and cholesterol secretion in bile was studied in unanaesthetized dogs fitted with a Thomas duodenal cannula. 2. Lysine acetylsalicylate induced a marked increase in bile flow and a parallel increase in erythritol clearance although the bile salt secretion remained unchanged; this suggests that the compound stimulated the formation of the canalicular (hepatocytic) bile salt-independent fraction of bile flow. 3. Lysine acetylsalicylate induced a significant decrease in biliary phospholipid and cholesterol secretion and the cholesterol saturation of bile was significantly reduced. 4. It is postulated that the decrease in phospholipid and cholesterol secretion resulted from the dilution of intracanalicular bile salts. This effect of lysine acetylsalicylate, and possibly of other bile salt-independent choleretics, may be of value in the treatment of cholesterol gallstones in man.

Biliary transport of cholephilic dyes: evidence for two different pathways.

1977 ◽  
Vol 232 (5) ◽  
pp. E445 ◽  
Author(s):  
J L Mahu ◽  
P Duvaldestin ◽  
D Dhumeaux ◽  
P Berthelot
Keyword(s):  
Bile Salt ◽  
Rose Bengal ◽  
Biliary Excretion ◽  
Bile Flow ◽  
Bile Salts ◽  
Experimental Conditions ◽  
Hepatobiliary Transport ◽  
Salt Excretion ◽  
Sodium Dehydrocholate

The hepatobiliary transport of three structurally related phthaleins was compared in the rat, and found to differ to a large extent in three experimental conditions: 1) after a 72-h fast; 2) after a 4-day phenobarbital treatment; and 3) during infusion of bile salts: sodium dehydrocholate or taurocholate. In the fasting group, bile flow and bile salt excretion (on a whole liver basis) decreased by 49 and 41%, respectively; bromsulphthalein sodium (BSP) and dibromsulphthalein sodium (DBSP) transport maximum (Tm) were reduced by 59 and 50%; however, rose bengal (RB) Tm remained normal. Phenobarbital pretreatment yielded a 44 and 29% increase in BSP and DBSP Tm, respectively, whereas RB Tm remained unchanged. Dehydrocholate infusion caused a 27 and 49% increase in BSP and DBSP Tm, whereas RB Tm increased by 12%. On the contrary, equimolar taurocholate infusion yielded a more important increase in RB Tm (56%) than in BSP and DBSP (31 and 22% respectively). It is suggested that RB does not share the same liver-to-bile excretory pathway as that of the former molecules. Our results emphasize the difficulties in predicting the biliary excretion of foreign compounds, even when their structure is closely similar.

scholarly journals Selective biliary lipid secretion at low bile-salt-output rates in the isolated perfused rat liver. Effects of phalloidin

1986 ◽  
Vol 237 (1) ◽  
pp. 301-304 ◽  
Author(s):  
K Rahman ◽  
R Coleman
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Biliary Lipid ◽  
Perfusion Fluid ◽  
Lipid Secretion ◽  
Rat Livers ◽  
Secretion Rates ◽  
Salt Secretion

At high bile-salt-secretion rates the biliary secretion of phospholipids and cholesterol is dependent on that of the bile salts. However, at low bile-salt outputs some secretion remains. Isolated perfused rat livers were used in these experiments in order to study the bile-salt-independent secretion of biliary lipids. The livers were isolated and saline (0.9% NaCl), or phalloidin dissolved in saline, was added to the perfusion fluid after 1 h of liver isolation. The concentration and output of cholesterol was significantly decreased in phalloidin-treated livers compared with the controls, whereas there was no significant decrease in phospholipids; the secretion of cholesterol and phospholipids can thus be uncoupled from each other by the action of phalloidin. These experiments suggest that a proportion of cholesterol gets into bile independently of bile salts and phospholipids. These findings are discussed in relation to the supersaturation of some biles with cholesterol and its relationship to the bile-salt-independent fraction of cholesterol.

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