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

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.

1989 ◽  
Vol 256 (1) ◽  
pp. R276-R280 ◽  
Author(s):  
T. Gerardo-Gettens ◽  
B. J. Moore ◽  
J. S. Stern ◽  
B. A. Horwitz

Lactation in the rat is marked by pronounced hyperphagia and suppression of brown fat (BAT) thermogenic capacity. We previously examined the possibility that elevated prolactin levels mediate these changes. The present study evaluated the effect of varying prolactin levels on food intake, BAT mitochondrial GDP binding, and carcass adiposity. Female rats were injected daily for 10 days with ovine prolactin at one of three doses: high = 3.0, medium = 1.0, or low = 0.3 micrograms/g body wt. Controls were injected with 0.9% NaCl. A group of uninjected rats served as an additional control. Cumulative food intake was significantly elevated in a dose-dependent manner in the prolactin-treated animals relative to the saline-injected and uninjected controls. Compared with the saline controls, the mean cumulative food intake was greatest at the high dose (20% increase), intermediate at the medium dose (17%), and smallest at the low dose (12%). Prolactin-treated rats gained significantly more weight during the experiment than did controls. Despite the hyperphagia in the prolactin-treated rats, no significant differences in BAT mitochondrial GDP binding were observed among the five groups. These data indicate that elevated prolactin levels stimulate food intake in a dose-dependent manner and that this hyperphagia is not accompanied by an increase in BAT mitochondrial GDP binding.


2012 ◽  
Vol 302 (9) ◽  
pp. G1035-G1042 ◽  
Author(s):  
Frank A. J. A. Bodewes ◽  
Marjan Wouthuyzen-Bakker ◽  
Marcel J. Bijvelds ◽  
Rick Havinga ◽  
Hugo R. de Jonge ◽  
...  

Cystic fibrosis liver disease (CFLD) is treated with ursodeoxycholate (UDCA). Our aim was to evaluate, in cystic fibrosis transmembrane regulator knockout ( Cftr −/−) mice and wild-type controls, whether the supposed therapeutic action of UDCA is mediated via choleretic activity or effects on bile salt metabolism. Cftr −/− mice and controls, under general anesthesia, were intravenously infused with tauroursodeoxycholate (TUDCA) in increasing dosage or were fed either standard or UDCA-enriched chow (0.5% wt/wt) for 3 wk. Bile flow and bile composition were characterized. In chow-fed mice, we analyzed bile salt synthesis and pool size of cholate (CA). In both Cftr −/− and controls intravenous TUDCA stimulated bile flow by ∼250% and dietary UDCA by ∼500%, compared with untreated animals ( P < 0.05). In non-UDCA-treated Cftr −/− mice, the proportion of CA in bile was higher compared with that in controls (61 ± 4 vs. 46 ± 4%; P < 0.05), accompanied by an increased CA synthesis [16 ± 1 vs. 10 ± 2 μmol·h−1·100 g body wt (BW)−1; P < 0.05] and CA pool size (28 ± 3 vs. 19 ± 1 μmol/100 g BW; P < 0.05). In both Cftr −/− and controls, UDCA treatment drastically reduced the proportion of CA in bile below 5% and diminished CA synthesis (2.3 ± 0.3 vs. 2.2 ± 0.4 μmol·day−1·100 g BW−1; nonsignificant) and CA pool size (3.6 ± 0.6 vs. 1.5 ± 0.3 μmol/100 g BW; P < 0.05). Acute TUDCA infusion and chronic UDCA treatment both stimulate bile flow in cystic fibrosis conditions independently from Cftr function. Chronic UDCA treatment reduces the hydrophobicity of the bile salt pool in Cftr −/− mice. These results support a potential beneficial effect of UDCA on bile flow and bile salt metabolism in cystic fibrosis conditions.


1978 ◽  
Vol 55 (4) ◽  
pp. 399-406 ◽  
Author(s):  
R. J. Vonk ◽  
E. Scholtens ◽  
J. H. Strubbe

1. In unanaesthetized, freely moving rats, which displayed a circadian rhythm in bile flow, hepatic transport of dibromosulphthalein was investigated at midnight when bile flow was high and at noon when bile flow was lower. The influence of pentobarbital anaesthesia and starvation on hepatic transport of dibromosulphthalein was also studied. The influence of bile salts on the hepatic transport process was investigated by interruption of the enterohepatic circulation. 2. Maximal biliary transport of dibromosulphthalein was subject to circadian variations: the biliary transport maximum at night was 25% higher than at noon, although maximal biliary concentration was not significantly altered. The distribution volume was increased by 21% during the night, but the primary hepatic clearance constant was not changed. 3. Pentobarbital anaesthesia decreased the maximal biliary concentration and the maximal biliary excretion rate of dibromosulphthalein, but the primary hepatic clearance constant was not changed. 4. Starvation for 48 h changed the primary hepatic clearance constant as well as the biliary excretion of dibromosulphthalein. 5. Interruption of the enterohepatic circulation of bile did not change the primary hepatic clearance constant of dibromosulphthalein, but decreased biliary excretion of the drug. 6. This study clearly indicates that time of the day, feeding conditions, the use of anaesthetics and interruption of the enterohepatic circulation of bile are important determinants in biliary excretion of cholephilic dyes.


1990 ◽  
Vol 68 (1) ◽  
pp. 136-138 ◽  
Author(s):  
Francis R. Sutherland ◽  
Roy M. Preshaw ◽  
Eldon A. Shaffer

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.


1983 ◽  
Vol 245 (1) ◽  
pp. G157-G163
Author(s):  
C. A. Garberoglio ◽  
H. M. Richter ◽  
A. Henarejos ◽  
A. R. Moossa ◽  
A. L. Baker

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.


1996 ◽  
Vol 270 (5) ◽  
pp. G804-G812 ◽  
Author(s):  
T. Yamada ◽  
M. Hoshino ◽  
T. Hayakawa ◽  
Y. Kamiya ◽  
H. Ohhara ◽  
...  

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.


1975 ◽  
Vol 229 (5) ◽  
pp. 1427-1437 ◽  
Author(s):  
KJ Ho ◽  
JL Drummond

Rats with chronic biliary drainage under a rigid lighting schedule (light on at 6 A.M. and off at 6 P.M.) exhibited a remarkable circadian rhythm of bile flow, biliary concentrations and excretory rates of bile salts, cholesterol, and phospholipid. The peak was attained at midnight and nadir at noon except for the peak concentrations of cholesterol and phospholipid occurring at 8 P.M. Cholesterol feeding abolished the circadian rhythm of biliary cholesterol and phospholipid concentrations but not their excretory rates because the daily fluctuation of the bile flow remained unchanged. Bilateral vagotomy enhanced the bile flow rate and shifted the peak of circadian rhythm of all parameters except bile salt 4 h earlier. Bilateral adrenalectomy abolished the circadian variation of the concentration of cholesterol and phospholipid and minimized that of bile salt, but the daily fluctuation of their excretory rates persisted in a lower amplitude. The studies suggested that such circadian rhythm might be controlled simultaneously by multiple factors and could not be entirely abolished by any single special treatment.


1951 ◽  
Vol 7 (3) ◽  
pp. 280-287 ◽  
Author(s):  
J. T. EAYRS

The growth and food consumption of mature female rats and of lactating rats and their litters reared under various conditions of illumination have been measured. Mature female rats grew less when kept in the dark than in the light. Newborn rats reared in total darkness by does which were allowed in the light for only 1½ hr. daily grew less during the first 18 days of life than their litter-mate controls. Newborn rats reared under natural lighting by does with both eyes removed did not grow as well as litter-mates reared by does with one eye removed. The mean weight of food eaten daily by mature female rats when in the dark did not differ significantly from that eaten when in natural lighting. Lactating does and their litters confined in total darkness and bilaterally enucleated does ate significantly less food than their controls. The reduction in food intake was apparent by the third day after parturition. On the other hand, when the doe received 1½ hr. illumination daily, the daily food intake of the experimental litters was depressed only during the latter part of lactation. The discussion suggests a possible way in which the effects of darkness on the normal adult female rat and on the lactating rat may be interrelated.


1989 ◽  
Vol 96 (4) ◽  
pp. 1142-1150 ◽  
Author(s):  
Paola Loria ◽  
Nicola Carulli ◽  
Giuseppe Medici ◽  
Alberto Tripodi ◽  
Rossella Iori ◽  
...  

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