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At least 307 records · Page 17Linked to original sources
PubMed1992

Effects of secretin on bile production in two kinds of cholestatic models by choledocho-caval fistula and bile duct ligation in rats.

Secretin is known to stimulate bile flow from the bile duct epithelium. To investigate the effects of secretin in cholestasis, we studied the response of the bile flow and the excretion of biliary components to secretin using two cholestatic models with or without damage to the bile duct epithelium. The model without bile duct epithelial damage was a choledocho-caval (CC) fistula over a 24-hour period, and the model with bile duct damage was a bile duct ligation over a 48-hour period. Secretin was administered by intravenous infusion for 30 minutes and bile was collected for 120 minutes. Controls were given saline similarly. The bile flow and biliary bicarbonate excretion rate were significantly increased after secretin infusion in the CC fistula rats when compared with the control rats, but no stimulation by secretin was observed in the ligated rats. These data indicate that secretin-induced bile production was enhanced under cholestatic conditions with no bile duct epithelial disturbance.

Animals↗
PubMed1995

Infusion of bile from methylene dianiline-treated rats into the common bile duct injures biliary epithelial cells of recipient rats.

Methylene dianiline (4,4'-diaminodiphenylmethane, DAPM) rapidly causes cholestasis and injury to biliary epithelial cells (BEC) in the liver and common bile duct of rats. Our objective was to determine if the proximate toxicant(s) was present in bile. Bile from DAPM-treated or control rats was infused through the common bile duct of untreated rats via inflow and outflow cannulas for 4 h. Cholestasis, increases in serum constituents, and intrahepatic BEC injury in the livers of DAPM-treated donor rats at 4 h were comparable to previous studies (Kanz et al., Toxicol. Appl. Pharmacol. 117 (1992) 88-97). BEC injury in the common bile duct of rats receiving DAPM bile or control bile was assessed by point counting. Percent necrosis was > 28% in the common bile duct of rats receiving DAPM bile compared to < 5% in rats receiving control bile. These results indicate that bile is a major route of BEC exposure to DAPM proximate toxicant(s) and demonstrate the utility of a new method for investigating mechanisms of biliary toxicants.

Aniline Compounds↗
PubMed2002

Sirolimus/cyclosporine/tacrolimus interactions on bile flow and biliary excretion of immunosuppressants in a subchronic bile fistula rat model.

The new immunosuppressive agent sirolimus generally is combined in transplant patients with cyclosporine and tacrolimus which both exhibit cholestatic effects. Nothing is known about possible cholestatic effects of these combinations which might be important for biliary excretion of endogenous compounds as well as of immunosuppressants. Rats were daily treated with sirolimus (1 mg kg(-1) p.o.), cyclosporine (10 mg kg(-1) i.p.), tacrolimus (1 mg kg(-1) i.p.), or a combination of sirolimus with cyclosporine or tacrolimus. After 14 days a bile fistula was installed to investigate the effects of the immunosuppressants and their combinations on bile flow and on biliary excretion of bile salts, cholesterol, and immunosuppressants. Cyclosporine as well as tacrolimus reduced bile flow (-22%; -18%), biliary excretion of bile salts (-15%;-36%) and cholesterol (-15%; -47%). Sirolimus decreased bile flow by 10%, but had no effect on cholesterol or bile salt excretion. Combination of sirolimus/cyclosporine decreased bile flow and biliary bile salt excretion to the same extent as cyclosporine alone, but led to a 2 fold increase of biliary cholesterol excretion. Combination of sirolimus/tacrolimus reduced bile flow only by 7.5% and did not change biliary bile salt and cholesterol excretion. Sirolimus enhanced blood concentrations of cyclosporine (+40%) and tacrolimus (+57%). Sirolimus blood concentration was increased by cyclosporine (+400%), but was not affected by tacrolimus. We conclude that a combination of sirolimus/tacrolimus could be the better alternative to the cotreatment of sirolimus/cyclosporine in cholestatic patients and in those facing difficulties in reaching therapeutic ranges of sirolimus blood concentration.

Animals↗
PubMed1987

Solubilization of lipids from hamster bile-canalicular and contiguous membranes and from human erythrocyte membranes by conjugated bile salts.

We have demonstrated in vitro the efficacy of the taurine-conjugated dihydroxy bile salts deoxycholate and chenodeoxycholate in solubilizing both cholesterol and phospholipid from hamster liver bile-canalicular and contiguous membranes and from human erythrocyte membrane. On the other hand, the dihydroxy bile salt ursodeoxycholate and the trihydroxy bile salt cholate solubilize much less lipid. The lipid solubilization by the four bile salts correlated well with their hydrophobicity: glycochenodeoxycolate, which is more hydrophobic than the tauro derivative, also solubilized more lipid. All the dihydroxy bile salts have a threshold concentration above which lipid solubilization increases rapidly; this correlates approximately with the critical micellar concentration. The non-micelle-forming bile salt dehydrocholate solubilized no lipid at all up to 32 mM. All the dihydroxy bile acids are much more efficient at solubilizing phospholipid than cholesterol. Cholate does not show such a pronounced discrimination. Lipid solubilization by chenodeoxycholate was essentially complete within 1 min, whereas that by cholate was linear up to 5 min. Maximal lipid solubilization with chenodeoxycholate occurred at 8-12 mM; solubilization by cholate was linear up to 32 mM. Ursodeoxycholate was the only dihydroxy bile salt which was able to solubilize phospholipid (although not cholesterol) below the critical micellar concentration. This similarity between cholate and ursodeoxycholate may reflect their ability to form a more extensive liquid-crystal system. Membrane specificity was demonstrated only inasmuch as the lower the cholesterol/phospholipid ratio in the membrane, the greater the fractional solubilization of cholesterol by bile salts, i.e. the total amount of cholesterol solubilized depended only on the bile-salt concentration. On the other hand, the total amount of phospholipid solubilized decreased with increasing cholesterol/phospholipid ratio in the membrane.

Animals↗
PubMed1991

Bile flow analysis by hepatobiliary scintigraphy in the terminal bile duct in patients with congenital malformations of the pancreatico-biliary ductal system.

The authors employed hepatobiliary scintigraphy (HBS), to study a dynamic state of bile stasis in the common bile duct and bile flow through the papilla of Vater in patients with congenital malformations of the pancreatico-biliary ductal system, such as congenital cystic dilatation of the common bile duct (CCDB) and anomalous arrangement of the pancreatico-biliary ductal system (AAPB). The HBS data were evaluated by a cholestatic index (CI), as an indicator of bile stasis in the common bile duct, and passage time (PT), as an indicator of bile flow through the papilla of Vater. CI was significantly higher in CCDB (3.67 +/- 0.92), in AAPB (2.87 +/- 0.28) and in both CCDB and AAPB with symptoms (2.86 +/- 0.59), compared with patients without CCDB or AAPB (0.96 +/- 0.41). PT was prolonged only in patients with AAPB with/without CCDB (greater than 30 minutes) compared to patients without AAPB (less than 12 minutes). This result suggested that bile stasis in the common bile duct was caused by a pooling of bile in the dilated common bile duct in CCDB, and by a disturbance of bile flow through the papilla of Vater in AAPB.

Aspartate Aminotransferases↗
PubMed1992

Interrelationships of bile acid and phospholipid fatty acid species with cholesterol saturation of duodenal bile in health and gallstone disease.

The relative amount of cholesterol and the fatty acid composition of phosphatidylcholines in bile can be influenced by the bile acid species secreted. To search for a contribution of secondary bile acids and of phosphatidylcholines to supersaturation of bile in gallstone disease, we compared the relative amount of cholesterol and the biliary composition of bile acids and of phospholipid fatty acids in cholecystokinin-stimulated duodenal bile of 22 female gallstone patients and 16 healthy controls and analyzed the interrelationships of these bile constituents. Gallstone patients had higher molar percentages of cholesterol than did controls (10.2 +/- 3.2 vs. 6 +/- 1.5 mol%; p less than 0.001) and demonstrated a trend toward larger fractions of deoxycholic and lithocholic acids. By linear models, variation of cholesterol saturation could be predicted (p less than 0.001) up to 53% by the bile acid pattern and up to 81% by the fatty acid pattern of phospholipids. Linear path analysis (goodness-of-fit index = 0.973) confirmed the tight relationship between phospholipid fatty acids (positive: oleic, arachidonic; negative: linoleic, palmitoleic) and the relative amount of cholesterol; more than half the influence of cholic, deoxycholic and lithocholic acids on the relative amount of cholesterol could be explained indirectly by their influence on the phospholipid fatty acid pattern. We conclude that the relationships examined by path analysis support the working hypothesis that secondary bile acids contribute to supersaturation of bile mainly by changing the fatty acid pattern of the secreted phospholipids (presumably the pattern of phosphatidylcholines), which increases the molar ratio of cholesterol/phospholipids in bile.

Adult↗
PubMed1997

Bile acid-independent bile flow is differently regulated by glucagon and secretin in humans after orthotopic liver transplantation.

The present study characterizes recovery of bile secretion after orthotopic liver transplantation (OLT) in humans with special regard to hormonal regulation of bile acid-independent bile flow by glucagon and secretin. Sixty-seven patients with an uncomplicated postoperative course were studied during the first 3 weeks after OLT to determine normalization of bile flow. A group of 7 and 10 patients, respectively, underwent a biliary stimulation test by either glucagon at days 7, 14, and 21 after OLT or by secretin at days 2, 10, and 21 after OLT. Secretin tests were similarly performed in patients with acute severe rejection during the first 10 days after OLT, while glucagon tests were performed in patients with acute allograft rejection occurring 2 weeks after OLT. Furthermore, hormone effects were studied in nontransplanted patients after cholecystectomy with indwelling biliary T tube. After OLT, bile secretory function recovered and stabilized within 14 days after surgery by reconstitution of both bile acid-dependent and -independent bile flow. Two weeks after OLT, bile secretion was comparable with nontransplanted patients after cholecystectomy. Glucagon and secretin stimulated bile acid-independent bile flow in transplanted and nontransplanted patients significantly, yet secretin choleresis, unlike glucagon choleresis, had already occurred during the first days after OLT and was unaffected by acute allograft rejection. These results allow the speculation that, in humans, glucagon and secretin exert their choleretic activity by different mechanisms and/or at different anatomical sites in the liver. Assuming that secretin acts at the bile duct cells, its secretory capacity was not altered by the transplantation procedure and during moderate or severe rejection episodes, as opposed to glucagon choleresis, which most likely originates in the hepatocytes and requires an entirely reconstituted canalicular transport system after OLT.

Acute Disease↗
PubMed1978

Bile acids LVIII. Bile acids and colorectal cancer.

Significant correlations have been reported by epidemiologists between the mortality from colorectal cancer in various populations and the consumption of meat or lipids by these populations. These have directed considerable attention to possible relationships between diet and the occurrence of this neoplasm. We have carried out studies of the composition of bile from rats as influenced by diets of varying lipid content. Two cannulas were surgically implanted to form an externalized bile duct through which bile was drained from the common duct and returned to the duodenum. Small aliquots were analyzed for total bile acids by enzymatic assay and for individual bile acids by high-pressure liquid chromatography, gas chromatography and gas chromatography-mass spectometry. Animals consuming diets highest in lipid content provided bile with the greatest amounts of bile acids. The primary bile acids, taurocholic, taurochenodeoxychilic, and tauro alpha- and beta-muricholic acids made up more than 99% of the 3 alph-hydroxy bile acids and were found in approximate molar ratio of 2:1:1. Either complete drainage of bile without return to the duodenum, or biliary tract obstruction had pronounced influence on the rate of secretion of bile and its composition.

Animal Feed↗
PubMed2004

A case of benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma.

We report a patient with benign bile duct stricture causing difficulty in differential diagnosis from bile duct carcinoma. A 66-year-old woman consulted a local physician because of general fatigue. Blood biochemical tests showed increased levels of biliary tract enzymes. Abdominal ultrasonography (US) revealed tapering and blockage of the midportion of the bile duct and dilation of the intrahepatic bile ducts. Magnetic resonance cholangiopancreatography (MRCP) demonstrated obstruction of the midportion of the bile duct. Later, because a marked increase in biliary tract enzymes and jaundice appeared, percutaneous transhepatic biliary drainage (PTBD) was performed. Post-PTBD cytological examination of bile was negative for cancer. A third biopsy showed slight hyperplasia with no malignant findings. Recholangiography, performed through PTBD, suggested gradual improvement of bile duct stricture, but could not completely exclude the possibility of malignancy; thus, resection of the bile duct including the stricture site was performed, and the resected specimen was submitted for intraoperative frozen section examination. Histopathological diagnosis did not reveal malignant findings. After cholecystectomy and bile duct resection, hepaticojejunostomy (Roux-en-Y) was performed. Because only erosion and desquamation of the mucosal epithelium and mild submucosal inflammatory cell infiltration and fibrosis were observed, chronic cholangitis was diagnosed histopathologically. Surgical resection of the bile duct should be considered for potentially malignant stricture of the bile duct.

Aged↗
PubMed1985

Heterogeneity of rabbit hepatocytes for bile secretion after acinar zone 3 damage induced by bromobenzene. Effect of bilirubin and bile salt infusions.

Anaesthetized rabbits were used to study the effect of bromobenzene-induced hepatic damage to the acinar zone 3 on bile flow, bile salt, sodium secretion as well as bilirubin transport in basal conditions or with infusion of sodium glycodeoxycholate. The bromobenzene-pretreated animals exhibited in basal conditions a lower bile flow (44%) than that of the controls, with a smaller decrease in bile salt output (27%) and sodium output (29%), whereas no modification in endogenous bilirubin excretion was observed. The bile salt independent fraction of secretion (BSIF) was reduced significantly after the toxic lesion both in terms of absolute and relative values. The hepatocytes of the periportal zone were capable of excreting the totality of bilirubin presented to the liver, regardless of the extent of bile flow or the input of bile salts. The infusion of bilirubin at 1.0 mumole/kg/min led to a fall in bile flow which was attributed to the interference of the pigment with the BSIF. The maximal bilirubin excretion was significantly smaller in bromobenzene-pretreated animals than in the controls, which could be due to the incapacity of the intoxicated rabbits to recruit quiescent hepatocytes. When glycodeoxycholate was administered under conditions of maximal bilirubin transport, bile flow increased as did bile salt secretion in both controls and animals with damaged livers. However, clear differences persisted between the two, which could be attributed not only to the volume fraction of necrosis but also to an interference by bilirubin with the hepatic handling of bile salts. Maximal bilirubin excretion increased in a similar way in both groups after glycodeoxycholate administration. It is proposed that glycodeoxycholate infusion facilitates the hepatic depletion of bilirubin, probably by stimulating transport processes.

Animals↗
PubMed1995

Model bile and bile salts accelerate mucin secretion by cultured dog gallbladder epithelial cells.

BACKGROUND & AIMS: Hypersecretion of gallbladder mucin has been proposed as a pathogenic factor in gallstone formation. We investigated whether mucin secretion is modulated by biliary constituents using normal, well-differentiated dog gallbladder epithelial cells. METHODS: Model biles or bile salts were applied to monolayers of epithelial cells. Mucin secretion was studied by measuring the secretion of [3H]N-acetyl-D-glucosamine-labeled glycoproteins. RESULTS: Model biles with different cholesterol saturation indices increased mucin secretion by the cells to an average 251% after 5 hours of incubation (P < 0.01). Mucin secretion remained elevated during a 24-hour period, suggesting a sustained effect on mucin secretion. There was no relation between the cholesterol or phospholipid concentration and the extent of stimulation of mucin secretion. Taurocholate caused a dose-dependent increase in mucin secretion, suggesting that bile salt was the bile component responsible for the stimulatory effect. At a concentration of 0.5 mmol/L, only the more hydrophobic bile salts taurochenodeoxycholate and taurodeoxycholate, but not the hydrophylic bile salts taurocholate and tauroursodeoxycholate, stimulated mucin secretion (P < 0.01). CONCLUSIONS: Bile salts play an important role in the regulation of mucin secretion. A shift in the bile salt composition of bile towards the more hydrophobic bile salts may cause mucin hypersecretion, thereby initiating cholesterol gallstone formation.

Animals↗
PubMed1991

Studies on the mechanism of bile salt-independent bile flow impairment in streptozotocin-induced hepatotoxicity.

The main factors involved in the impairment of formation of the bile salt-independent bile flow (BSIF) in streptozotocin (SZ)-treated rats were examined. Twenty-four hours after SZ injection (50 mg/kg body wt, i.v.) bile flow, bile salt output and biliary excretion of the major inorganic electrolytes (sodium, chloride and bicarbonate) were significantly diminished. The relationship between bile flow and bile salt output obtained during the administration of sodium taurocholate at stepwise-increasing rates indicated that bile salt-independent bile flow (y-intercept) was diminished by 37% in SZ-treated rats. The relationship between electrolyte output and bile salt output showed that the fractions of sodium, chloride and bicarbonate excreted independently of bile salt (y-intercept) decreased to 59%, 47% and 67% of the control values respectively, while the amount of electrolyte secreted per unit of bile salt secreted was unaffected in SZ-treated rats. The hepatic activity of Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) was decreased by 59% (P less than 0.05) in SZ-treated rats. Nicotinamide administered prior to SZ prevented the hyperglycemia indicative of SZ-induced diabetes, but had no effect on the decrease in Na+,K(+)-ATPase activity caused by the drug. These results suggest that SZ itself, and not its diabetogenic effect, decreases the BSIF by a mechanism that involves impairment of the biliary electrolyte excretion, which could be the result of the inhibition of the hepatic Na+,K(+)-ATPase activity.

Animals↗
PubMed2004

Measurement of bile acid in serum and bile with arylamine-glass-bound 3alpha-hydroxysteroid dehydrogenase and diaphorase.

3Alpha-hydroxysteroid dehydrogenase (3-HSD) from Pseudomonas testosteroni and diaphorase (lipoyl dehydrogenase) from Clostridium spp. have been immobilized individually onto arylamine glass beads through diazotization. A cost-effective enzymic colorimetric method for determination of bile acid in serum and bile employing a mixture of these immobilized enzymes was developed. The method is based on measurement of reduced nicotinamide adenine dinucleotide generated from bile acid in serum/bile by immobilized 3alpha-HSD with a color reagent consisting of nitro blue tetrazolium chloride salt, oxidized nicotinamide adenine dinucleotide, and immobilized lipoyl dehydrogenase in 0.065 M sodium phosphate buffer, pH 7.0. Analytical recovery of added bile acid (50 and 200 micromol/L) was 95.57 and 85.46% in serum and 97.6 and 91.6% in bile, respectively. Within- and between-batch coefficients of variation (CV) for bile acid determination were <1.2 and <0.2% in serum and >0.1 and <0.1% in bile, respectively. Good correlations for bile acid in serum (r1=0.92) and in bile (r2=0.97) were obtained by use of a standard chemical method and the present method. The mixture of immobilized 3alpha-HSD dehydrogenase and lipoyl dehydrogenase lost 50% of its initial activity after 6 months of regular use. The cost of bile acid determination in 100 serum and bile samples by the present method has been compared with that of the Sigma kit method.

3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)↗
PubMed1984

Development and validation of a method for measuring the glycine and taurine conjugates of bile acids in bile by high-performance liquid chromatography.

We developed and validated a simple method for measuring the individual glycine and taurine conjugates of bile acids in bile by high-performance liquid chromatography with a C18 reversed-phase column using an isocratic solvent system of acidified methanol--potassium phosphate. Without preliminary derivatization or purification, complete separation of the ten major conjugated bile acids present in bile could be achieved in 65 min. Total bile acid concentrations were identical when measured enzymatically and by summing the individual bile acids determined by high-performance liquid chromatography. Bile acid composition determined by gas-liquid chromatography correlated with results by high-performance liquid chromatography. Finally, measurements of individual glycine and taurine conjugates in human bile and in mixtures of bile acid standards by high-performance liquid chromatography and thin-layer chromatography gave similar results. This high-performance liquid chromatographic system permits simultaneous quantification of total and individual bile acids and their glycine and taurine conjugates in bile.

Bile↗
PubMed1976

A study of the physicochemical interactions between biliary lipids and chlorpromazine hydrochloride. Bile-salt precipitation as a mechanism of phenothiazine-induced bile secretory failure.

Since chlorpromazine hydrochloride [2-chloro-10-(3-dimethylaminopropyl)-phenothiazine hydrochloride] is commonly implicated in causing bile-secretory failure in man and is secreted into bile, we have studied the physicochemical interactions of the drug with the major components of bile in vitro. Chlorpromazine hydrochloride molecules are amphiphilic by virtue of possessing a polar tertiary amine group linked by a short paraffin chain to a tricyclic hydrophobic part. At pH values below the apparent pK (pK'a 7.4) the molecules are water-soluble cationic detergents. We show that bile salts in concentrations above their critical micellar concentrations are precipitated from solution by chlorpromazine hydrochloride as insoluble 1:1 salt complexes. In the case of mixed bile-salt/phosphatidylcholine micellar solutions, however, the degree of precipitation is inhibited by the phospholipid in proportion to its mole fraction. With increases in the concentration of chlorpromazine hydrochloride or bile salt, micellar solubilization of the precipitated complexes results. Sonicated dispersions of the negatively charged phospholipid phosphatidylserine were also precipitated, but dispersions of the zwitterionic phospholipid phosphatidylcholine were not. Chlorpromazine hydrochloride efficiently solubilized these membrane phospholipids as mixed micellar solutions when the drug:phospholipid molar ratio reached 4:1. Polarizing-microscopy and X-ray-diffraction studies revealed that the precipitated complexes were amorphous and potentiometric studies confirmed the presence of a salt bond. Some dissociation of the complex occurred in the case of the most polar bile salt (Ks 0.365). As canalicular bile-salt secretion determines much of bile-water flow, we propose that complexing and precipitation of bile salts by chlorpromazine hydrochloride and its metabolites may be physicochemically related to the reversible bile-secretory failure produced by this drug.

Animals↗
PubMed1977

Effects of bile and bile acids on cultured human fibroblasts.

Impaired healing induced by leakage of bile has been postulated as one factor responsible for complications after reconstructive bile duct surgery. The cytotoxicity of human bile and its major bile acids on cultured human fibroblasts was therefore studied by evaluation of their effects on cell morphology and growth, on synthesis and secretion of 35SO4-mucopolysaccharides and on release of a lysosomal enzyme. Normal human fibroblasts derived from a standard culture strain (MRC-5) were grown to confluence and exposed to: (1) sterile human T-tube bile, (2) a mixture of bile acids resembling that of human bile, or (3) various concentrations of the glycine- and taurine conjugates of cholic, chenodeoxycholic or deoxycholic acid. Medium containing whole bile (total bile acid concentration 0.25, 0.75 or 1.6 mmol/l) exerted time and dose dependent cytotoxic effects on morphology and growth and release of lysosomal enzyme. Synthesis and secretion of 35SO4-mucopolysaccharides were markedly inhibited. The bile acid mixture exhibited the same time and dose dependent effects. The conjugates of deoxycholic acid were found to be the most toxic of the individual bile acids studied.

Bile↗
PubMed1994

Apparent selective bile acid malabsorption as a consequence of ileal exclusion: effects on bile acid, cholesterol, and lipoprotein metabolism.

A new model has been developed to characterise the effect of a standardised ileal exclusion on bile acid, cholesterol, and lipoprotein metabolism in humans. Twelve patients treated by colectomy and ileostomy for ulcerative colitis were studied on two occasions: firstly with a conventional ileostomy and then three months afterwards with an ileal pouch operation with an ileoanal anastomosis and a protective loop ileostomy, excluding on average 95 cm of the distal ileum. The ileostomy contents were collected during 96 hours and the excretion of bile acids and cholesterol was determined using gas chromatography-mass spectrometry. Fasting blood and duodenal bile samples were collected on two consecutive days. After the exclusion of the distal ileum, both cholic and chenodeoxycholic acid excretion in the ileostomy effluent increased four to five times without any change in cholesterol excretion. Serum concentrations of lathosterol (a marker of cholesterol biosynthesis) and 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) were increased several fold. Plasma concentrations of total VLDL triglycerides were also increased whereas the concentrations of total and LDL cholesterol, and apolipoprotein B were decreased. There were no changes in biliary lipid composition or cholesterol saturation of bile. The results show that the exclusion of about 95 cm of distal ileum causes malabsorption of bile acids but apparently not of cholesterol. The bile acid malabsorption leads to increased synthesis of both bile acids and cholesterol in the liver. It is suggested that bile acids can regulate cholesterol synthesis by a mechanism independent of the effect of bile acids on cholesterol absorption. The enhanced demand for cholesterol also leads to a decrease in plasma LDL cholesterol and apolipoprotein B concentrations. The malabsorption of bile acids did not affect biliary lipid composition or cholesterol saturations of VLDL triglycerides.

Adult↗
PubMed1983

Canalicular bile salt-independent bile formation: concepts and clues from electrolyte transport in rat liver.

Studies on canalicular electrolyte transport are reviewed with reference to the concept that hepatocellular inorganic ion secretion may provide an osmotic drive for canalicular water flow. Cellular transport of electrolytes and of some nonelectrolytes appears directly or indirectly (cotransport or potential-sensitive transport) related to the activity of Na+-K+-ATPase of the sinusoidal cell membrane, but the role of the enzyme in regulating bile flow remains undetermined. Bile secretion of the isolated rat liver continues in the absence of either Na+, K+, Cl-, or HCO-3 when these ions are replaced in the perfusion medium by other permanent ions. Transepithelial salt concentration gradients, established experimentally, cause transient changes of bile flow and dissipate very quickly. Isotopic ion equilibration between sinusoids and bile proceeds faster than between sinusoids and liver cells. Both observations indicate extensive electrolyte diffusion through a paracellular shunt pathway. This pathway appears preferentially permeable to cations, and it restricts permeation of molecules of the size of sucrose (no apparent diffusion or effects of solvent drag) or bile acids (no backleak). In promoting canalicular osmotic water flow, transepithelial concentration gradients of NaCl are less effective than those of sucrose, revealing a reflection coefficient of NaCl of 0.3. By perfusion with hypertonic medium containing sucrose, bile flow is reduced. Bile production against this opposing osmotic gradient is accomplished by an increase in biliary organic anion concentration. Inorganic ion concentrations essentially conform to a Gibbs-Donnan distribution across the canalicular epithelium, established by the presence of impermeant anions in bile. Hence, the luminal electrical potential is expected to be negative with respect to the sinusoids. It is concluded that biliary secretion of endogenous organic anions is the major osmotic driving force for canalicular bile salt-independent bile flow and that transport of inorganic ions into bile results mainly from diffusion and solvent drag.

Animals↗