Pentobarbital Inhibits the Biliary Excretion of Organic Acids: a Study with Succinylsulfathiazole in the Rat

1975 ◽  
Vol 53 (3) ◽  
pp. 470-474 ◽  
Author(s):  
D. G. Bailey ◽  
H. Paul ◽  
G. E. Johnson
Keyword(s):  
Organic Acids ◽  
Biliary Excretion ◽  
Concentration Gradient ◽  
Bile Flow ◽  
Hepatic Transport ◽  
Acidic Drugs ◽  
Time Period ◽  
Liver Concentration

The present study was undertaken to determine whether the use of pentobarbital as an anesthetic reduces the biliary excretion of acidic drugs in rats. The drug chosen for the experiment was succinylsulfathiazole, a compound excreted unmetabolized in the bile. Animals anesthetized with urethane excreted 22.1% of the dose in the bile as compared to only 8.4% for the same time period in pentobarbital anesthetized animals. The choice of anesthetic did not affect the bile flow but did influence the bile/liver concentration gradient of succinylsulfathiazole, with the pentobarbital treated rats demonstrating a significantly lower value. Despite the higher biliary excretion of succinylsulfathiazole in the urethane treated rats, the total amount in the bile plus urine was 60% of the dose in the urethane anesthetized animals as compared with 62% in the pentobarbital treated rats. These results suggest that pentobarbital reduced the hepatic transport of succinylsulfathiazole into the bile. The question whether urethane is a preferred anesthetic for biliary excretion studies warrants further investigation.

Biliary Excretion of Dibromosulphthalein in the Freely Moving Unanaesthetized Rat: Circadian Variation and Effects of Deprivation of Food and Pentobarbital Anaesthesia

1978 ◽  
Vol 55 (4) ◽  
pp. 399-406 ◽  
Author(s):  
R. J. Vonk ◽  
E. Scholtens ◽  
J. H. Strubbe
Keyword(s):  
Biliary Excretion ◽  
Bile Flow ◽  
Enterohepatic Circulation ◽  
Circadian Variation ◽  
Hepatic Clearance ◽  
Circadian Variations ◽  
Hepatic Transport ◽  
Freely Moving ◽  
Biliary Excretion Rate ◽  
Pentobarbital Anaesthesia

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.

Influence of bile salts on hepatic transport of dibromosulphthalein.

1979 ◽  
Vol 237 (6) ◽  
pp. E524
Author(s):  
R J Vonk ◽  
M Danhof ◽  
T Coenraads ◽  
A B van Doorn ◽  
K Keulemans ◽  
...  
Keyword(s):  
Biliary Excretion ◽  
Bile Flow ◽  
Bile Salts ◽  
Ethacrynic Acid ◽  
Organic Anion ◽  
Hepatic Uptake ◽  
Hepatic Transport ◽  
Intracellular Binding ◽  
Highly Correlated ◽  
Biliary Excretion Rate

The influence of bile salts on hepatic transport of the organic anion dibromosulphthalein (DBSP) was investigated in rats. Bile salts influence the hepatic uptake, intracellular binding, and biliary excretion of DBSP. The overall effect depends on the administered dose of bile salts and DBSP. High doses of bile salts inhibited hepatic uptake of DBSP, whereas low doses of bile salts stimulated bile flow and simultaneously increased maximal biliary excretion of DBSP. The uncharged nonbile salt choleretic ouabain also stimulated biliary DBSP excretion. In contrast, the anionic nonbile salt choleretics, ethacrynic acid and theophylline, did not stimulate biliary excretion of DBSP. Because DBSP inhibited biliary excretion of ethacrynic acid and its metabolites, the lack of a stimulatory effect of ethacrynic acid choleresis might be explained by concomitant inhibition of biliary excretion of DBSP, masking the stimulatory effect of ethacrynic acid. Biliary transport maximum of DBSP was highly correlated with bile flow. The biliary clearance (Vmax/Km) was only moderately changed by bile salt administration, whereas the increase in the maximal biliary excretion rate was more pronounced, implying that the apparent Km for biliary excretion of DBSP was also increased by the bile salts. It is inferred that the stimulation of net biliary excretion of DBSP by bile salts may be due to a diminished transport from bile into the hepatocytes as the consequence of the decreased biliary concentration caused by the choleresis.

Sex Differences of Hepatic Conjugation of Bilirubin Determine its Maximal Biliary Excretion in Non-Anaesthetized Male and Female Rats

1983 ◽  
Vol 64 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Maurizio Muraca ◽  
Jan De Groote ◽  
Johan Fevery
Keyword(s):  
Biliary Excretion ◽  
High Performance ◽  
Relative Proportion ◽  
Female Rats ◽  
Male Rats ◽  
Transferase Activity ◽  
Hepatic Transport ◽  
Male And Female Rats ◽  
Udp Glucuronosyltransferase ◽  
Rate Limiting

1. Hepatic bilirubin UDP-glucuronosyltransferase activity was higher in female than in male rats; gonadectomy decreased enzyme activity in females and increased it in males. This sex difference in bilirubin conjugation was further used to evaluate the effect of differences in conjugation on the maximal biliary excretion of bilirubin in the non-anaesthetized rat. 2. After infusion of bilirubin, the maximal biliary excretory rate (Tm) and maximal concentration of bilirubin in bile were respectively 70% and 40% higher in female than in male rats; these values were decreased in females after ovariectomy and increased in males after orchiectomy. A linear relationship was found (r = 0.86; P < 0.001) between bilirubin Tm and hepatic bilirubin UDP-glucuronosyltransferase activity in the four groups of rats, suggesting that conjugation was the rate-limiting step for the maximal hepatic transport of bilirubin. 3. At the end of bilirubin infusion, bilirubin conjugates in serum, determined by alkaline methanolysis and high-performance liquid chromatography, ranged from 0.5 to 1.4% of total bilirubin. Therefore no significant reflux of conjugated bilirubin occurred during saturation of the hepatic transport of the pigment, once more suggesting that the secretory step was not rate-limiting. 4. The composition of bilirubin conjugates in bile was similar in the four groups of rats, despite significant differences in transferase activity. This suggests that the relative proportion of bilirubin mono- and di-conjugates in bile is affected by factors other than transferase activity alone. Relatively more monoconjugates were excreted under the bilirubin load than in basal conditions.

Relationship of Bile Salts and Bile Flow to Biliary Excretion of Iopanoic Acid

1972 ◽  
Vol 7 (1) ◽  
pp. 11-15
Author(s):  
Albert A. Moss ◽  
John R. Amberg ◽  
Scott R. Jones
Keyword(s):  
Biliary Excretion ◽  
Bile Flow ◽  
Bile Salts ◽  
Iopanoic Acid ◽  
Relationship Of

Hepatic transport and biliary excretion of sulfobromophthalein in aflatoxin B1-treated rats

1985 ◽  
Vol 77 (2) ◽  
pp. 353-357 ◽  
Author(s):  
Maria C. Carrillo ◽  
Joaquín V. Rodriguez ◽  
Juan A. Monti ◽  
Emilio A. Rodriguez Garay
Keyword(s):  
Aflatoxin B1 ◽  
Biliary Excretion ◽  
Hepatic Transport

The bile flow and biliary excretion of ursocholate in the rat

Life Sciences ◽  
1983 ◽  
Vol 33 (24) ◽  
pp. 2377-2386 ◽  
Author(s):  
Kenichi Kitani ◽  
Setsuko Kanai ◽  
Yuko Sato ◽  
Kiyoshisa Uchida
Keyword(s):  
Biliary Excretion ◽  
Bile Flow

Biliary excretion of dye in dogs infused with BSP or its glutathione conjugate

1976 ◽  
Vol 231 (2) ◽  
pp. 399-407 ◽  
Author(s):  
JL Barnhart ◽  
B Combes
Keyword(s):  
Biliary Excretion ◽  
Bile Flow ◽  
Additional Mechanism ◽  
Glutathione Conjugate ◽  
Canalicular Bile ◽  
Transport Carrier ◽  
Per Se ◽  
Osmotic Activity ◽  
Conjugated Metabolites

A comparison of the maximal rates of biliary excretion (Tm), of dye in dogs infused with either BSP or its glutathione conjugate (BSP-GSH) was carried out. Tm was much higher when BSP-GSH rather than BSP was infused. This was accounted for by a significantly higher concentration of dye in bile of dogs receiving BSP-GSH. Evidence is presented that BSP and its conjugated metabolites compete for a common transport carrier and that BSP disproportionately depresses the biliary excretion of conjugated dye compounds. This latter observation accounts for the depressed dye Tm found during infusion of BSP. Choleresis invariably accompanied dye excretion. When BSP-GSH was infused, enhanced bile flow could be accounted for by the predicted osmotic activity of dye transported into bile. By contrast, the choleresis measured during infusion of BSP was significantly greater than that predicted. An additional mechanism for choleresis is operative, therefore, when unconjugated BSP is infused. Administration of taurocholate enhanced dye Tm when BSP-GSH was infused. Since increments of canalicular bile flow induced by theophylline and glucagon did not enhance dye excretion into bile, this effect by taurocholate appears to be related to taurocholate excretion per se rather than to the enhanced canalicular bile flow which accompanies its excretion.

Intracellular alkalinization stimulates bile flow and vesicular-mediated exocytosis in IPRL

1993 ◽  
Vol 265 (2) ◽  
pp. G347-G353 ◽  
Author(s):  
R. Bruck ◽  
A. Benedetti ◽  
M. Strazzabosco ◽  
J. L. Boyer
Keyword(s):  
Horseradish Peroxidase ◽  
Biliary Excretion ◽  
Bile Flow ◽  
Channel Blocker ◽  
Rat Hepatocytes ◽  
Disulfonic Acid ◽  
K Channel ◽  
Rat Livers ◽  
Intracellular Alkalinization ◽  
Stimulation Of

Intracellular pH recovery from an acute alkaline load in rat hepatocytes is mediated by a Cl(-)-HCO3- exchanger, which is electroneutral, Na+ independent, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) sensitive. Stimulation of this Cl(-)-HCO3- exchanger requires intact microtubules, suggesting that vesicular transport may be required to activate this exchanger. To determine if intracellular alkalinization stimulates biliary HCO3- excretion and bile flow in the intact liver by vesicle-mediated exocytosis, isolated perfused rat livers (IPRL) were alkalinized by two protocols. Isohydric changes in CO2 and HCO3- concentrations induced transient increases in bile flow by 36% (P < 0.01), which were abolished by DIDS (0.01 mM), inhibited by pretreatment with colchicine (P = 0.01), but not affected by membrane depolarization with the K(+)-channel blocker BaCl2 (1 mM). Similarly, perfusion with 20 mM NH4Cl produced a 42% increase in bile flow (P < 0.01) and a 26% increase in biliary HCO3- excretion. Both the increases in bile flow and HCO3- excretion were almost completely blocked by DIDS and inhibited by pretreatment with colchicine (P < 0.01). Biliary excretion of horseradish peroxidase was also increased during intracellular alkalinization with either protocol (P < 0.01). These findings suggest that intracellular alkalinization stimulates bile flow and biliary HCO3- excretion. Microtubule-dependent vesicular-mediated exocytosis is involved in this response.

ENHANCED BILIARY THYROXINE EXCRETION IN RATS TREATED WITH PREGNENOLONE-16α-CARBONITRILE

1976 ◽  
Vol 81 (1) ◽  
pp. 110-119 ◽  
Author(s):  
M. M. Japundžić ◽  
C. H. Bastomsky ◽  
I. P. Japundžić
Keyword(s):  
Thyroid Hormone ◽  
Biliary Excretion ◽  
Clearance Rate ◽  
Bile Flow ◽  
Stomach Tube ◽  
Biliary Clearance ◽  
Gunn Rats ◽  
Peripheral Metabolism ◽  
Hormonal Release ◽  
Serum Tsh

ABSTRACT Normal rats were treated with pregnenolone-16α-carbonitrile (PCN) 10 mg/100 g by stomach tube twice daily for 3 days. In these animals the biliary excretion of intravenously injected 125I-thyroxine (T4) was enhanced and the bile: plasma 125I ratio (B/P ratio) and the biliary clearance rate of plasma 125I-T4 was increased. Normal rats were treated with PCN for 3 days and homozygous Gunn rats for 13 days. In both groups PCN enhanced the bile flow and elevated the B/P ratios and the biliary clearance rate of plasma T4 following ip injection of 125I-T4 17 h previously. PCN-treatment had no effect on the fractions of biliary 125I present as T4-glucuronide, T4 and I− in either the normal or Gunn rats. Treatment with PCN for 10 days produced goitres in normal and Gunn rats and in normal rats elevated the serum TSH (bioassay) levels and the 17 h thyroid 131I uptake as well as the serum PB125I concentrations, without affecting stable PBI concentrations. These data indicated increased pituitary TSH release in response to increased peripheral metabolism of thyroid hormone; enhanced hormonal release from the thyroid kept pace with the accelerated peripheral loss.

scholarly journals Biliary excretion of [14C]succinylsulphathiazole in the rat and rabbit

1967 ◽  
Vol 105 (3) ◽  
pp. 1295-1299 ◽  
Author(s):  
M M Abou-el-Makarem ◽  
P Millburn ◽  
R L Smith
Keyword(s):  
Intravenous Injection ◽  
Biliary Excretion ◽  
Concentration Gradient ◽  
Bile Salts ◽  
Liver Cells ◽  
Simultaneous Administration ◽  
The Poor ◽  
Two Factors

1. After intravenous injection about 30% of the dose (20mg./kg.) of succinylsulphathiazole is excreted unchanged in the bile in 3hr. by the rat, whereas only about 1% is excreted by the rabbit. When the renal pedicles are ligated the biliary excretion of succinylsulphathiazole in the rat increases to about 80% of the dose, but in the rabbit under these conditions the biliary excretion is only 2% of the dose. 2. In the rat, the sulphonamide readily enters the liver and biliary excretion occurs against a concentration gradient from liver to bile; further, the excretory process can be saturated, and can be depressed by the simultaneous administration of phenolphthalein glucuronide or bile salts. 3. In the rabbit, these conditions have not been found; succinylsulphathiazole does not readily enter the liver from the plasma, there is no transfer of the drug from the liver cells to the bile against a concentration gradient, and no saturation or depression of the biliary excretion of succinylsulphathiazole is found. 4. It is suggested that two factors responsible, at least partly, for the low biliary excretion of succinylsulphathiazole in the rabbit are the poor entry of the sulphonamide into the liver in this species and a deficiency of the concentrative mechanism for its excretion in the bile.

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