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.

Fasting and postprandial hepatic bile flow in unanesthetized opossums

1990 ◽  
Vol 259 (5) ◽  
pp. G745-G752 ◽  
Author(s):  
I. Takahashi ◽  
M. K. Kern ◽  
W. J. Dodds ◽  
W. J. Hogan ◽  
R. D. Layman ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Flow ◽  
Common Duct ◽  
Enterohepatic Circulation ◽  
Phase Iii ◽  
Hepatic Bile ◽  
Bipolar Electrodes ◽  
Motor Complex ◽  
The Common ◽  
The Relationship

In conscious opossums, we evaluated the relationship between hepatic bile flow and the intestinal motor function during fasting as well as after feeding. In six opossums, bipolar electrodes were implanted from the gastric antrum to the terminal ileum. After cholecystectomy, the common duct was ligated, and a catheter was tied into the proximal common duct for collecting hepatic bile. During subsequent studies, hepatic bile flow was measured, and bile was returned to the duodenum through an externalized duodenal catheter. Cyclic increases in bile flow during fasting did not show a close correlate with the duodenal migratory motor complex (MMC) cycle. Rather, bile flow showed peak values [0.11 +/- 0.02 (SE) ml/min] when phase III MMC activity reached the midileum. Hepatic bile flow correlated closely with the amount of bile acid secreted by the liver. When the bile acid pool was depleted by diverting bile from the intestine, hepatic secretion of bile fell to uniformly low values of approximately 0.04 ml/min that did not show cyclic variation. Hepatic bile flow after feeding increased to a maximal value of 0.12 +/- 0.01 ml/min at 90 min. We conclude that increases in hepatic bile flow during fasting and after meals are determined mainly by variations in intestinal motor activity that alter small bowel transit and thereby affect the enterohepatic circulation of bile acids.

Bile Secretion and Bile Composition in the Freely Moving, Unanaesthetized Rat with a Permanent Biliary Drainage: Influence of Food Intake on Bile Flow

1978 ◽  
Vol 55 (3) ◽  
pp. 253-259 ◽  
Author(s):  
R. J. Vonk ◽  
A. B. D. van Doorn ◽  
J. H. Strubbe
Keyword(s):  
Food Intake ◽  
Bile Salt ◽  
Bile Flow ◽  
Circadian Variation ◽  
Bile Secretion ◽  
Female Rats ◽  
Bile Composition ◽  
Influence Of Food ◽  
The Mean ◽  
Freely Moving

1. In freely moving, unanaesthetized rats bile flow was measured continuously over the whole day-night cycle. Bile composition was analysed and the influence of food intake on bile flow was investigated. 2. In both sexes a distinct circadian variation of bile production was observed. The mean night-time production was 50% higher than the day-time value for female rats and 38% for male rats. In the morning when the light was switched on, a sharp decrease in secretion rate was prominent and bile flow gradually increased in the afternoon. 3. The pattern of food intake was positively correlated with the pattern of bile secretion. During fasting only the general level of bile flow decreased, but the circadian variation persisted. Refeeding again increased the mean level of bile flow. 4. The chenodeoxycholate/cholate ratio in these rats with permanent bile fistulae was higher than in rats with ‘acute’ bile fistulae and changed during the day-night cycle. The ratio decreased from 1.01 at 05.00 hours to a minimum of 0.41 at 15.00 hours. 5. During the day-night cycle the sodium, potassium, calcium and cholesterol concentrations were relatively constant. The total bile salt concentration was only slightly changed, so that both the bile salt-dependent fraction and the bile salt-independent fraction were subject to about the same circadian variations.

Effect of insulin on canalicular bile formation

1976 ◽  
Vol 231 (1) ◽  
pp. 40-43 ◽  
Author(s):  
RS Jones
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Intravenous Infusion ◽  
Bile Flow ◽  
Sodium Taurocholate ◽  
Duodenal Fistula ◽  
Bile Formation ◽  
Biliary Clearance ◽  
The Common ◽  
Bicarbonate Output

Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of gastric and duodenal cannulas. The common bile duct was cannulated through the duodenal fistula. After bile flow had been stabilized by intravenous infusion of sodium taurocholate the dogs were given an intravenous injection of insulin or 0.9% NaCl (control). Insulin caused marked increases in bile flow, chloride output, and biliary clearance of erythritol and small increases in bicarbonate output and bile salt output. The increased erythritol clearance indicates that canalicular secretion contributes to insulin choleresis in dogs.

scholarly journals A quantitative investigation into the enterohepatic circulation of bile salts in the cat

1938 ◽  
Vol 126 (844) ◽  
pp. 287-302 ◽  
Keyword(s):  
Bile Duct ◽  
Bile Salts ◽  
Enterohepatic Circulation ◽  
Taurocholic Acid ◽  
Fistulous Opening ◽  
Duodenal Fistula ◽  
Quantitative Investigation ◽  
Glycocholic Acid ◽  
The Common ◽  
Made In

In 1870 Schiff put forward his hypothesis of the enterohepatic circulation of the bile. He observed that if a large fistulous opening be made in dogs between the surface of the abdomen and the gall bladder without the common bile duct being ligatured, the bile flows externally. If, however, the fistulous opening is closed, then the bile flows into the intestine. Using dogs with “amphibolic” fistulae Schiff found that the quantity of bile obtained from such fistulae was much greater immediately after the bile had been allowed to flow into the intestine than when it had been flowing externally. The part played by bile salts in this phenomenon he established by the introduction of bile salts into the intestine through a duodenal fistula. This procedure increased both the quantity of bile and the amount of bile salts secreted. The circulation of the bile salts has been confirmed by many observers. Weiss (1884) fed glycocholic acid to dogs and found the corresponding acid in the bile subsequently excreted, although dog's bile normally contains taurocholic acid only.

Pancreatic secretion in rat: effect of bile stasis and of bile salt

1962 ◽  
Vol 203 (1) ◽  
pp. 60-62 ◽  
Author(s):  
Y. Kuroyanagi ◽  
H. Necheles
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Common Bile Duct ◽  
Bile Salt ◽  
Pancreatic Secretion ◽  
Bile Secretion ◽  
Clinical Implications ◽  
Bile Stasis ◽  
Sodium Dehydrocholate ◽  
The Common

Obstruction of the common bile duct in the rat (albino, Rockland strain) stimulated pancreatic secretion beginning several hours after obstruction, and lasting as long as 7 days. Bile acid (sodium dehydrocholate) injected intraperitoneally did not change basal pancreatic secretion, but did increase bile secretion. When secretin injection was followed by bile acid, there was a marked increase over the secretin-stimulated secretion. Clinical implications of this mechanism are discussed.

Apparent volume of the biliary tree in the dog

1979 ◽  
Vol 57 (5) ◽  
pp. 524-528 ◽  
Author(s):  
James L. Barnhart ◽  
Burton Combes
Keyword(s):  
Bile Flow ◽  
Bolus Injection ◽  
Common Duct ◽  
Biliary Tree ◽  
Apparent Volume ◽  
Mean Value ◽  
Maximal Concentration ◽  
A Value ◽  
The Common ◽  
The Mean

The apparent volume of the biliary tree (ABV) in the dog was determined by measuring the mean biliary transit time of injected [14C]taurocholate ([14C]TC). After bolus injection of [14C]TC, entry of bile salt into the lumen of the biliary tree is signaled by an increase in bile flow. The volume of bile collected at the common duct from onset of choleresis until maximal concentration of 14C radioactivity is reached in bile minus the calculated quantity of bile that contains radioactivity and the cannula volume yields a value for the volume of the biliary tree present just prior to injection of [14C]TC. The mean value for ABV in 19 dogs was 2.49 ± 0.65 μL/g liver (mean ± SD).

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.

Pharmacological and physiological doses of insulin and determinants of bile flow in dogs

1983 ◽  
Vol 245 (1) ◽  
pp. G157-G163
Author(s):  
C. A. Garberoglio ◽  
H. M. Richter ◽  
A. Henarejos ◽  
A. R. Moossa ◽  
A. L. Baker
Keyword(s):  
Portal Vein ◽  
Bile Salt ◽  
Bile Flow ◽  
Plasma Insulin ◽  
Sodium Taurocholate ◽  
Bile Secretion

The role of insulin in control of bile secretion is uncertain. To study the mechanism of choleresis produced by large doses of insulin, bile was collected through modified Thomas cannulas from dogs anesthetized with pentobarbital. Animals received pipenzolate methylbromide, sodium taurocholate, and [14C]erythritol. After bile flow had stabilized three animals received infusions of insulin at 2, 4, 13, 26, 35, and 70 mU . kg-1 . min-1 for 40 min each. Bile and [14C]erythritol clearance increased (P less than 0.005), but bile salt output remained constant, suggesting that the choleresis was mainly due to enhanced bile salt-independent canalicular flow. Plasma insulin and glucagon levels also rose when insulin was infused. To exclude the possible effects of glucagon three additional animals received somatostatin (800 ng . kg-1 . min-1) along with infusions of insulin. Bile flow and [14C]erythritol clearance again increased significantly, but glucagon levels remained low, suggesting that the effects on bile flow were due to insulin alone. To determine whether physiological doses of insulin altered bile flow dogs were anesthetized with pentobarbital and received pipenzolate methylbromide, taurocholate, [14C]erythritol, and somatostatin (800 ng . kg-1 . min-1). Insulin (0.2 and 0.8 mU . kg-1 . min-1) was infused through the portal vein for 1 h each. Bile flow and [14C]erythritol clearance increased with insulin (0.8 mU . kg-1 . min-1; P less than 0.02), suggesting that the choleresis may have been due to bile salt-independent canalicular flow. Plasma insulin rose to physiological postprandial levels. These studies demonstrate that pharmacological and physiological levels of insulin administered to dogs produce a significant choleresis. Thus insulin may play an important role in the regulation of bile secretion.

scholarly journals ON THE EXPULSION OF BILE BY THE GALL BLADDER; AND A RECIPROCAL RELATIONSHIP WITH THE SPHINCTER ACTIVITY

1926 ◽  
Vol 44 (2) ◽  
pp. 173-198 ◽  
Author(s):  
Philip D. McMaster ◽  
Robert Elman
Keyword(s):  
Gall Bladder ◽  
Biliary Tract ◽  
Common Duct ◽  
Bile Secretion ◽  
Reciprocal Relationship ◽  
Maximum Pressure ◽  
The Common ◽  
Pressure Resistance ◽  
The One ◽  
Considerable Pressure

After feeding a dog, forceful contractions of the gall bladder occur that are sufficient in strength to expel part of the contents of the viscus against a considerable pressure resistance. The pressure within the gall bladder of a healthy, unanesthetized dog fasted 24 to 48 hours is usually about equal to a column of bile 100 mm. high. After a few swallows of food there is a rapid increase in the pressure to more than 200 mm. with a gradual fall in it again, and repeated similar rises and falls occur thereafter. The gall bladder contractions responsible for these alterations are accompanied by a lessening in the resistance to the passage of bile to the intestine, a resistance which is maintained by the muscles at the lower end of the common duct. There would appear to be a reciprocal response on the part of the two structures to the one stimulus. The maximum pressure developing within the temporarily obstructed biliary tract in an animal with the gall bladder excluded about equals that of a column of bile slightly more than 300 mm. in height. The taking of food acts as a stimulus on the rate of bile secretion, but does not alter the maximum secretion pressure. When the gall bladder is connected with the duct system, obstruction does not lead until after some hours to the development of a pressure of more than 100 to 150 mm. within the biliary tract,—that is to say the pressure does not rise above the normal. Its failure to rise further is referable to the activity of the gall bladder to store and concentrate the bile as secreted. The physiological and clinical significance of these findings is discussed.

Bile secretion in rats with indomethacin-induced intestinal inflammation

1996 ◽  
Vol 270 (5) ◽  
pp. G804-G812 ◽  
Author(s):  
T. Yamada ◽  
M. Hoshino ◽  
T. Hayakawa ◽  
Y. Kamiya ◽  
H. Ohhara ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Flow ◽  
Intestinal Inflammation ◽  
Acid Output ◽  
Bile Secretion ◽  
Pool Size ◽  
Secretory Function ◽  
Indomethacin Treatment

The objective of this study was to characterize the bile secretion, including the composition of biliary bile acids, bile salt pool size, and transcytotic vesicle transport, in a rat model of subacute intestinal inflammation induced by indomethacin. Indomethacin treatment significantly decreased bile acid-independent bile flow and biliary secretion of bile acid and cholesterol, while increasing biliary phospholipid output in vivo. Although indomethacin treatment did not change the bile salt pool size in vivo, alpha- and beta-muricholic acids were significantly deceased and hyodeoxycholic and deoxycholic acids were increased in bile. Bile flow and the transport maximum of taurocholate did not decrease, and biliary horseradish peroxidase output was significantly enhanced in isolated perfused livers from indomethacin-treated rats. Endotoxin in the portal blood was significantly increased in rats treated with indomethacin. Clindamycin slightly reduced intestinal inflammation but significantly prevented decreases in bile flow, bile acid output, and transport maximum of taurocholate. We conclude that, although biliary secretory function was apparently decreased in vivo, that of hepatocyte function was maintained in this model.

Sign in / Sign up

Export Citation Format

Share Document