Bile-salt-dependent and independent choleresis induced by bucolome in the rat

1977 ◽  
Vol 55 (5) ◽  
pp. 1155-1161 ◽  
Author(s):  
K. Kitani ◽  
Y. Morita ◽  
R. Miura ◽  
S. Kanai
Keyword(s):  
Bile Salt ◽  
Flow Rate ◽  
Bile Flow ◽  
Enterohepatic Circulation ◽  
Excretion Rate ◽  
Intestinal Content ◽  
Intestinal Wall ◽  
Salt Excretion ◽  
Male Wistar Rats ◽  
Bile Flow Rate

Choleresis induced by bucolome (BC) (1-cyclohexyl-5-n-butyl-2,4,6-trioxoperhydropyrimidine) was studied in male Wistar rats. [14C]Erythritol and mannitol clearance studies indicated this choleresis to be of canalicular origin. In 1-h continuous bile collection studies, immediately after the interruption of enterohepatic circulation (acute interruption), both bile flow and bile salt excretion rates were significantly increased in rats administered BC. However, the bile salt excretion rate fell rather rapidly in BC-administered rats, while the bile flow rate was fairly constant during this 1-h period. Thus, unlike the situation in control rats, bile flow rate was not significantly correlated with the bile salt excretion rate in BC-administered rats. In rats that had an external bile fistula open for 16–20 h (chronic interruption of enterohepatic circulation) the bile flow rate was also significantly increased by BC administration, while the bile salt excretion rate was not changed after BC administration.It is suggested that BC induced bile-salt-independent choleresis in both experimental rat groups (acute and chronic interruption of enterohepatic circulation). In addition, BC appeared to increase the bile-salt-dependent fraction of bile in rats with acute interruption of enterohepatic circulation, possibly by mobilizing the bile salt pooled in the intestinal content and (or) intestinal wall.

EFFECTS OF PHENOBARBITAL ON BILE SALT METABOLISM IN CHOLESTASIS DUE TO INTRAHEPATIC BILE DUCT HYPOPLASIA

PEDIATRICS ◽  
1973 ◽  
Vol 51 (6) ◽  
pp. 992-997
Author(s):  
Adolf Stiehl ◽  
M. Thaler ◽  
William H. Admirand
Keyword(s):  
Bile Duct ◽  
Bile Salt ◽  
Peripheral Blood ◽  
Bile Salts ◽  
Bile Ducts ◽  
Enterohepatic Circulation ◽  
Control Period ◽  
Intrahepatic Bile Duct ◽  
Total Serum ◽  
Salt Excretion

The effects of phenobarbital (PB) on bile salt metabolism in a patient with severe cholestasis due to congenital paucity of perilobular bile ducts were studied with 14C-cholate and 3H-chenodeoxycholate. During the control period (without PB) cholate was the predominant bile salt in the peripheral blood, whereas chenodeoxycholate was predominant in the total bile salt pool. This difference in the distribution of the two primary bile salts appeared to be caused by relatively greater impairment of excretion of cholate from the liver cell into the bile. PB administration caused a decrease in the total serum bile salt concentration (from 132 to 62µg/ml), in the total bile salt pool (from 412 to 304 mg) and in the biologic half-life (cholate from 106 to 34 hours; chenodeoxycholate from 77 to 42 hours). The proportion of the total bile salt pool present in the peripheral blood decreased from 16.8% to 11.7%. In addition, PB markedly increased the fecal bile salt excretion. These data suggest the PB improves pruritus in this type of intrahepatic cholestasis by reducing serum bile salt concentrations. This is accomplished by a shift in bile salts from the peripheral blood into the enterohepatic circulation and by enhancing fecal bile salt excretion.

Importance of bicarbonate in bile salt independent fraction of bile flow.

1978 ◽  
Vol 235 (2) ◽  
pp. E158 ◽  
Author(s):  
W G Hardison ◽  
C A Wood
Keyword(s):  
Bile Salt ◽  
Bile Flow ◽  
Transport Mechanism ◽  
Excretion Rate ◽  
Organic Anion ◽  
Weak Acid ◽  
Anion Transport ◽  
Bicarbonate Transport ◽  
Canalicular Membrane ◽  
Bile Canalicular Membrane

The bile salt independent fraction (BSIF) of canalicular bile flow from the isolated rat liver perfused with bicarbonate-free perfusate is 50% of that from the liver perfused with bicarbonate-containing perfusate. HCO3-excretion is nearly eliminated and Na+ and Cl- excretion is reduced 50%. Replacement of HCO3- into perfusate increased bile flow by 0.3 microliter/g.min without changing bile acid excretion rate. 5.5-Dimethyl-2,4-oxazolidinedione (DMO) produced a similar effect. DMO was passively distributed between bile and plasma. The data indicate that a bicarbonate transport mechanism is responsible for production of up to 50% of the BSIF. Another weak acid, N-5[5-(2-methoxyethoxy)-2-pyrimidinyl]sulfamoylbenzene (glymidine), was rapidly excreted into bile and increased bile flow by over 2.0 microliter/g.min. Glymidine is probably excreted by an independent organic anion transport mechanism, and any effect on the bicarbonate transport mechanism is obscured. Canaliculus-enriched hepatocyte membrane fractions contained no HCO3-stimulated ATPase activity. Either this enzyme is unimportant in hepatocyte bicarbonate transport or transport occurs across membranes other than the bile canalicular membrane.

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.

Resveratrol reduces matrix metalloproteinases and alleviates intrahepatic cholestasis of pregnancy in rats

2016 ◽  
Vol 94 (4) ◽  
pp. 402-407 ◽  
Author(s):  
Zhong Chen ◽  
Lingqing Hu ◽  
Mudan Lu ◽  
Zongji Shen
Keyword(s):  
Ursodeoxycholic Acid ◽  
Flow Rate ◽  
Intrahepatic Cholestasis ◽  
Bile Flow ◽  
Liver Disorder ◽  
Enzymatic Activities ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Resveratrol Treatment ◽  
Bile Flow Rate ◽  
Cholestasis Of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disorder occurring specifically in pregnancy, and matrix metalloproteinase (MMP)-2 and MMP-9 were found to be elevated in ICP patients. Using ethinylestradiol-induced ICP rats as the model, we examined the effect of resveratrol on ICP symptoms such as bile flow rate, serum enzymatic activities, and TBA concentration, as well as MMP levels, and compared with the known ICP drug ursodeoxycholic acid. Both MMP-2 and MMP-9 were upregulated in ICP rats, and resveratrol treatment could inhibit the elevation of both MMPs, whereas ursodeoxycholic acid did not exhibit any effect. Although ursodeoxycholic acid alleviated ICP symptoms, resveratrol treatment in general exhibited better outcome in restoring bile flow rate, serum enzymatic activities, and TBA concentration. Our results for the first instance strongly supported the potential of RE as a new therapeutic agent in treating ICP, possibly through inhibiting MMP-2 and MMP-9.

scholarly journals Effect of Pregnancy on the Excretion of Sulphobromophthalein in Bile

1972 ◽  
Vol 25 (5) ◽  
pp. 1101 ◽  
Author(s):  
HM Shaw ◽  
T Heath
Keyword(s):  
Oral Contraceptives ◽  
Flow Rate ◽  
Bile Flow ◽  
Plasma Clearance ◽  
Late Pregnancy ◽  
Oestrogen Treatment ◽  
Human Pregnancy ◽  
Normal Human ◽  
Bile Flow Rate

A decreased plasma clearance of sulphobromophthalein (BSP) is often observed during the latter half of normal human pregnancy (Tindall and Beazley 1965). It also occurs during the ingestion of oral contraceptives (Roman and Hecker 1968) and after treatment with oestrogens at doses similar to those produced daily in late pregnancy (Kappas 1968). A reduction in bile flow has been described after oestrogen treatment in rats (Javitt and Harkavy 1969; Forker 1969; Kreek et al. 1967), but no attempts appear to have been made to associate changes in bile flow rate with alterations in BSP excretion.

Bile Flow and Composition During Bile Acid Depletion and Administration

1974 ◽  
Vol 52 (2) ◽  
pp. 334-348 ◽  
Author(s):  
Curtis D. Klaassen
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Bile Flow ◽  
Enterohepatic Circulation ◽  
Acid Excretion ◽  
Bile Formation ◽  
Bile Acid Excretion ◽  
Rat Bile ◽  
Acid Administration

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.

scholarly journals The elements of fluid mechanics of bile flow through biliary drainage catheters

2019 ◽  
Vol 12 (1) ◽  
pp. 29-41
Author(s):  
Wenguang Li
Keyword(s):  
Reynolds Number ◽  
Obstructive Jaundice ◽  
Fluid Mechanics ◽  
Pressure Gradient ◽  
Friction Factor ◽  
Flow Rate ◽  
Bile Flow ◽  
Bile Flow Rate ◽  
Flow Through ◽  
Inner Diameter

Obstructive jaundice in the biliary tract can infect blood and result in mortality with a high rate. Percutaneous transhepatic biliary drainage (PTBD) with catheters is a useful solution discharging the obstructive jaundice. However, the elements of fluid mechanics showing clinical performance of a PTBD catheter have been documented little so far. In the article, empirical relationships between bile flow rate and pressure gradient in PTBD catheters were studied in terms of equivalent friction factor for the first time. Firstly, an equivalent friction factor in a catheter was raised and determined based on existing in vitro experimental data of bile flow through the catheters with different materials, various inner diameters and lengths under various pressure differences. Then, an empirical correlation of bile flow rate through a catheter was established based on pressure gradient, inner diameter and bile viscosity. The correlation was used to identify effects of catheter inner diameter and bile viscosity on the bile flow rate under the physiological bile pressure difference across obstructed common bile ducts. The feature of minor hydraulic losses in the catheters was clarified, too. The proposed equivalent friction factor was proportional to Reynolds number in a power of -0.654 in comparison with a power of -1 for the fully developed laminar flow in circular pipes. The bile flow rate through a catheter was proportional to inner diameter, kinematic viscosity, and pressure gradient in the powers of 3.2, -0.5 and 0.74, respectively. The minor hydraulic losses could be significant when Reynolds number was greater than 100.

Effect of glucagon on bile cAMP secretion

1980 ◽  
Vol 238 (2) ◽  
pp. G119-G123
Author(s):  
D. L. Kaminski ◽  
W. H. Brown ◽  
Y. G. Deshpande
Keyword(s):  
Bile Salt ◽  
Bile Flow ◽  
Enterohepatic Circulation ◽  
Camp Concentration ◽  
Cyclic Monophosphate ◽  
Camp Metabolism

The effect of bile flow and adenosine 3',5'-cyclic monophosphate (cAMP) secretion of substances that alter cAMP metabolism in other systems was evaluated. The experiments were performed on awake dogs with chronic biliary and gastric fistulas and on anesthetized rabbits prepared with acute bile fistulas. In all experiments the enterohepatic circulation was maintained by intravenous bile salt administration. In dogs, glucagon increased bile flow and bile cAMP secretion with 4 micrograms . kg-1 . h-1 increasing bile flow from control values of 273 +/- 27 to 413 +/- 6 microliters/min, whereas bile cAMP concentration rose from 3.9 +/- 0.9 to 12.1 +/- 1.1 nmol/ml. Theophylline in dogs increased bile flow while cAMP secretion decreased. Evaluation of the effects of theophylline on glucagon-stimulated bile flow suggest that both agents act by the same mechanism; however, theophylline did not significantly alter glucagon-stimulated increases in bile cAMP. In rabbits, glucagon increased bile cAMP secretion while bile flow was not significantly changed. Hormonal production of increased systemic or hepatic cAMP can increase bile cAMP unassociated with changes in bile flow. Based on the measurement of cAMP in bile the increase in glucagon-stimulated bile flow produced by theophylline is not cAMP mediated.

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