Metabolism of 4-C14-cholesterol in the isolated perfused rat liver

1962 ◽  
Vol 202 (4) ◽  
pp. 699-703 ◽  
Author(s):  
Henry Danielsson ◽  
William Insull ◽  
Paul Jordan ◽  
Ove Strand
Keyword(s):  
Bile Acids ◽  
Rat Liver ◽  
Chenodeoxycholic Acid ◽  
Liver Cholesterol ◽  
Tween 20 ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Mode Of Administration ◽  
Ethanol Extracts

The influence of the mode of administration on the distribution and oxidation of 4-C14-cholesterol in the isolated perfused rat liver has been studied. When labeled cholesterol was added to the perfusate as an emulsion with Tween 20 only about 1% of the labeled liver cholesterol was oxidized to bile acids. Approximately the same oxidation (1–2%) was obtained in perfusions of livers from animals injected with emulsions of 4-C14-cholesterol 1 hr before operation. When livers were perfused with blood withdrawn from animals injected with emulsions of 4-C14-cholesterol 24 hr prior to sacrifice the amount of labeled liver cholesterol converted to bile acids was about 10%, i.e., five to ten times more than in the above-mentioned sets of experiments, indicating the advisability of using physiological solutions of cholesterol rather than artificial emulsions. The main labeled acidic products were identified as cholic and chenodeoxycholic acid. The only labeled product isolated from ethanol extracts of the liver was found to be identical with cholesterol.

Uptake of bile acids by perfused rat liver

1976 ◽  
Vol 231 (3) ◽  
pp. 734-742 ◽  
Author(s):  
J Reichen ◽  
G Paumgartner
Keyword(s):  
Bile Acids ◽  
Rat Liver ◽  
Chenodeoxycholic Acid ◽  
Competitive Inhibition ◽  
Compartment Model ◽  
Hepatic Uptake ◽  
Perfused Rat Liver ◽  
Multiple Indicator Dilution ◽  
Rapid Injection ◽  
Carrier Mediated Transport

The uptake of 14C-labeled cholic, taurocholic, and chenodeoxycholic acid by the perfused rat liver was studied to characterize the mechanism responsible for hepatic uptake of bile acids. A rapid-injection multiple indicator-dilution technique and the three-compartment model of Goresky were employed. The kinetics of hepatic uptake of the three bile acids could be described by the Michaelis-Menten equation. The maximal uptake velocities (Vmax) were 24.9 +/- 2.2 (mean +/- SD), 20.8 +/- 1.2, 1.2, and 11.4 +/- 0.9 nmol/s-g liver for cholic, taurocholic, and chenodeoxycholic acid, respectively. The corresponding apparent half-saturation constants (Km) were 526 +/- 125, 258 +/- 43, and 236 +/- 48 nmol/g liver. Competitive inhibition could be demonstrated between cholate and taurocholate as well as between cholate and chenodeoxycholate. Substitution of 94% of the Na+ in the perfusion medium decreased the Vmax and the apparent Km of taurocholate uptake by 68 and 55%, respectively. These findings are consistent with the hypothesis that bile acids are taken up into the hepatocyte by Na+-dependent carrier-mediated transport.

Identification of Cholehepatic Recirculation of Bile Acids in Isolated Perfused Rat Liver

1988 ◽  
Vol 21 (1) ◽  
pp. 397-400
Author(s):  
G. Belforte ◽  
B. Bona ◽  
A.F. Hofmann ◽  
G. Molino
Keyword(s):  
Bile Acids ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver

Bile Acid Metabolism in Mammals. V. Studies on the Sex Difference in the Response of the Isolated Perfused Rat Liver to Chenodeoxycholic Acid

1973 ◽  
Vol 51 (6) ◽  
pp. 418-423 ◽  
Author(s):  
I. M. Yousef ◽  
R. Magnusson ◽  
V. M. Price ◽  
M. M. Fisher
Keyword(s):  
Bile Acid ◽  
Sex Difference ◽  
Rat Liver ◽  
Chenodeoxycholic Acid ◽  
Bile Acid Metabolism ◽  
Isolated Perfused Rat Liver ◽  
Base Line ◽  
Female Rat ◽  
Perfused Rat Liver ◽  
Perfusion Medium

The hepatic metabolism of chenodeoxycholic acid (CDCA) was studied using the isolated perfused rat liver technique. In 12 perfusions, six male and six female, 30 μmol of CDCA were added to the perfusion medium, and in 12 other perfusions, also six of each sex, 1 μmol of CDCA was added to the perfusion medium. The CDCA was added after 2 h of base-line perfusion and the bile acids of liver, plasma, and bile were analyzed by combined thin-layer and gas chromatography. In the 2 h of perfusion prior to the addition of exogenous CDCA there were sex differences in the kinetics of bile acid secretion in the bile and in the bile acid composition of that bile. Following the addition of CDCA to the perfusion medium the female liver was found to take up more CDCA from the perfusion medium, to store more CDCA, and to convert less CDCA to β-muricholic acid. It was documented that the toxicity of CDCA for the isolated perfused liver of the female rat is not due to α- or β-muricholic acid, the end products of CDCA metabolism in the rat. The relatively greater capacity of the male liver to convert potentially toxic CDCA to nontoxic β-muricholic acid may explain, at least in part, the observed sex difference in CDCA hepatotoxicity.

scholarly journals Transport of fluorescent bile acids by the isolated perfused rat liver: Kinetics, sequestration, and mobilization

Hepatology ◽  
1998 ◽  
Vol 28 (2) ◽  
pp. 510-520 ◽  
Author(s):  
Fernando Holzinger ◽  
Claudio D. Schteingart ◽  
Huong-Thu Ton-Nu ◽  
Carolina Cerrè ◽  
Joseph H. Steinbach ◽  
...  
Keyword(s):  
Bile Acids ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver

scholarly journals The synthesis of bile acids in perfused rat liver subjected to chronic biliary drainage

1970 ◽  
Vol 118 (3) ◽  
pp. 519-530 ◽  
Author(s):  
I. W. Percy-Robb ◽  
G. S. Boyd
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Rat Liver ◽  
Chenodeoxycholic Acid ◽  
Biliary Drainage ◽  
Specific Radioactivity ◽  
Mevalonic Acid ◽  
Liver Cholesterol ◽  
Microscopic Appearance

1. Isolated rat liver was perfused with heparinized whole blood under physiological pressure resulting in the secretion of bile at about the rate observed in vivo. 2. The preparation remained metabolically active for 4h and was apparently normal in function and microscopic appearance. 3. When the perfusate plasma and liver cholesterol pool was labelled by the introduction of [2-14C]mevalonic acid the specific radioactivity of the perfusate cholesterol increased. The biliary acids (cholic acid and chenodeoxycholic acid) were labelled and had the same specific radioactivity. 4. Livers removed from rats immediately after, and 40h after, the start of total biliary drainage, were perfused; increased excretion rates of both cholic acid and chenodeoxycholic acid were found when the liver donors had been subjected to biliary drainage. 5. The incorporation of [2-14C]mevalonic acid or rat lipoprotein labelled with [14C]cholesterol into bile acids was studied. 6. A dissociation between the mass of bile acid excreted and the rate of incorporation of 14C was found. This was attributed to the changing specific radioactivity of the cholesterol pool acting as the immediate bile acid precursor.

Transport of chenodeoxycholic acid and its 3-α- and 7-α-sulfates by isolated perfused rat liver

Hepatology ◽  
1990 ◽  
Vol 12 (4) ◽  
pp. 738-742 ◽  
Author(s):  
Ulrich Gärtner ◽  
Tobias Goeser ◽  
Adolf Stiehl ◽  
Richard Raedsch ◽  
Allan W. Wolkoff
Keyword(s):  
Rat Liver ◽  
Chenodeoxycholic Acid ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver
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