scholarly journals Mathematical modeling of the metabolic activity of an isolated perfused rat liver under reduced oxygenation of the perfusion medium

2018 ◽  
Author(s):  
K.V. Shadrin ◽  
V.G. Pakhomova ◽  
O.V. Kryukova ◽  
A.P. Rupenko
Keyword(s):  
Mathematical Modeling ◽  
Rat Liver ◽  
Metabolic Activity ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium

scholarly journals Metabolism of inorganic sulphate in the isolated perfused rat liver. Effect of sulphate concentration on the rate of sulphation by phenol sulphotransferase

1978 ◽  
Vol 176 (3) ◽  
pp. 959-965 ◽  
Author(s):  
Gerard J. Mulder ◽  
Katja Keulemans
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Rat Liver ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Physiological Concentration ◽  
Sulphate Concentration ◽  
Inorganic Sulphate

1. The metabolism of inorganic [35S]sulphate (Na235SO4) was studied in the isolated perfused rat liver at three initial concentrations of inorganic sulphate in the perfusion medium (0, 0.65 and 1.30mm), in relation to sulphation and glucuronidation of a phenolic drug, harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole). 2. [35S]Sulphate rapidly equilibrated with endogenous sulphate in the liver. It was excreted in bile and reached, at the lowest concentration in the perfusion medium, concentrations in bile that were much higher than those in the perfusion medium; at the higher sulphate concentrations, these concentrations were equal. The physiological concentration of inorganic sulphate in the liver, available for sulphation of drugs, is similar to the plasma concentration. 3. At zero initial inorganic sulphate in the perfusion medium, the rate of sulphation was very low and harmol was mainly glucuronidated. At 0.65mm-sulphate glucuronidation was much decreased and considerable sulphation took place, indicating efficient competition of conjugation by sulphation. At 1.30mm-sulphate the sulphation increased still further. 4. The results suggest that an important factor in sulphation is the relatively high Km of synthesis of adenosine 3′-phosphate 5′-sulphatophosphate (the co-substrate of sulphation) for inorganic sulphate, which is of the order of the plasma concentration of inorganic sulphate. The steady-state adenosine 3′-phosphate 5′-sulphatophosphate concentration may determine the rate of sulphate conjugation of drugs in the rat in vivo.

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.

Cadmium transport in isolated perfused rat liver: zinc-cadmium competition

1979 ◽  
Vol 236 (3) ◽  
pp. C139-C143 ◽  
Author(s):  
B. S. Kingsley ◽  
J. M. Frazier
Keyword(s):  
Rat Liver ◽  
Biliary Excretion ◽  
Cadmium Uptake ◽  
Molar Ratio ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Transport Pathway ◽  
Cadmium Transport ◽  
Excess Zinc

The hypothesis that one component of cadmium uptake by rat hepatocytes involves a mediated transport pathway normally operative for zinc transport was tested in the isolated perfused rat liver preparation. Excess zinc in the perfusion medium suppressed cadmium uptake as indicated by the decrease in the normalized clearance (initial clearance divided by liver weight) from 0.340 +/- 0.019 (ml/min)/g in the presence of normal zinc concentrations (Zn:Cd molar ratio, 1.6) to 0.138 +/- 0.017 (ml/min)/g (Zn:Cd molar ratio, 13.0). In excess-zinc control experiments (no cadmium present) little zinc is accumulated by the liver, apparently due to competition between intrahepatic and extracellular binding. Exposure to cadmium increases both zinc secretion into the perfusion medium and biliary excretion of zinc. The effect at the sinusoidal membrane is probably a result of both the blockage of zinc resorption during cadmium uptake and the displacement of intrahepatic zinc. The effect on biliary excretion of zinc is due solely to displacement of intrahepatic zinc. These results are consistent with the proposed hypothesis for cadmium transport.

Cell-swelling-induced taurine release from isolated perfused rat liver

1994 ◽  
Vol 72 (1-2) ◽  
pp. 8-11 ◽  
Author(s):  
H. S. Brand ◽  
A. J. Meijer ◽  
L. A. Gustafson ◽  
G. G. A. Jörning ◽  
A. C. J. Leegwater ◽  
...  
Keyword(s):  
Amino Acids ◽  
Rat Liver ◽  
Cell Swelling ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Liver Mass ◽  
Taurine Release ◽  
Perfusion Medium ◽  
Nacl Concentration ◽  
Isolated Liver

Astrocytes and lymphocytes are able to release significant amounts of taurine during periods of hypotonicity to reduce the increase in cell volume. To investigate this mechanism in the liver, we studied the release of free amino acids from isolated perfused rat liver during hypotonicity. The osmolarity of the perfusion medium was reduced from 305 to 255 or 205 mosM by decreasing the NaCl concentration 25 or 50 mM, respectively. This induced an 6–8% increase in liver mass and was associated with a specific 1.7-fold (−50 mosM) and 14-fold (−100 mosM) increase of the taurine release. None of the other amino acids measured showed a significant increase in their concentration in the effluent. The increase in taurine release occurred within 30 s after exposure to hypotonicity (maximal after 1–1.5 min) and followed closely the changes in liver mass. The taurine release declined gradually during successive exposures of the isolated liver to −100 mosM. This release was 29 and 17% of the original during the second and third exposure, respectively.Key words: cell swelling, liver, taurine.

Simultaneous perfusion of [4-14C]oestriol and [6,9-3H2]oestriol 16α-monoglucuronide through the isolated rat liver

1982 ◽  
Vol 100 (2) ◽  
pp. 274-278
Author(s):  
M. Höller ◽  
H. Weber ◽  
H. Breuer
Keyword(s):  
Rat Liver ◽  
Small Extent ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Isolated Rat Liver ◽  
Isolated Rat

Abstract. The uptake of [4-14C]oestriol by the isolated perfused rat liver is 3.8 times faster as compared to that of simultaneously perfused [6,9-3H2]oestriol 16α-monoglucuronide. During perfusion the concentration of both radioactive oestrogens decreased exponentially in perfusion medium (apparent kel: 0.061 min−1 and 0.016 min−1, respectively). [6,9−3H2]Oestriol 16α-monoglucuronide was metabolized only to a small extent; more than 92% was secreted unchanged into the bile where it was highly concentrated (1800 nmol/g). In contrast [4-14C]oestriol was extensively metabolized; it was mainly hydroxylated at C-atom 2, leading to a rapid increase in the concentration of 2-hydroxyoestriol in the perfused medium. This metabolite was quickly taken up by the liver during recirculation and subsequently either methylated or sulphated. 2-Hydroxyoestriol monosulphate was glucuronated to 2-hydroxyoestriol 16α-monoglucuronide 3-sulphate, which was rapidly excreted into the bile. No double conjugate was formed when [6,9-3H2]oestriol 16α-monoglucuronide was perfused; this is additional evidence for the correctness of the assumption that monoglucuronides cannot serve as precursors of sulphoglucuronides.

Effect of graded bilirubin loads on bilirubin transport by perfused rat liver

1976 ◽  
Vol 230 (3) ◽  
pp. 736-742 ◽  
Author(s):  
Bloomer ◽  
J Zaccaria
Keyword(s):  
Rat Liver ◽  
Extraction Efficiency ◽  
Unconjugated Bilirubin ◽  
Constant Infusion ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Hepatic Extraction ◽  
Perfusion Medium ◽  
Wide Range ◽  
Male Wistar Rats

Features of hepatic bilirubin transport were studied with the isolated perfused rat liver. Male Wistar rats weighing 350-400 g were used as liver donors. When bilirubin was constantly infused into the perfusion medium, which contained sheep erythrocytes and 3.0 g/100 ml bovine serum albumin, the maximal excretion rate for bilirubin was 14.4 +/- 1.2 mug/min per g liver. Over a wide range of constant bilirubin infusion rates which went as high as 25.9 mug/min per g liver, there was no effect on bile flow, bile acid excretion, or the pattern of bilirubin conjugates in bile. The hepatic extraction efficiency for unconjugated bilirubin from the perfusate also remained constant averaging 26%. However, when bolus injections of bilirubin were used to produce higher levels of unconjugated bilirubin in the perfusate than could be attained during constant infusion, the disappearance rate of [14C]bilirubin from the perfusate decreased with increasing bilirubin concentrations. This was consistent with saturation of the hepatic removal of unconjugated bilirubin.

The Effect of Changes in Lactate Uptake on the Intracellular pH of the Perfused Rat Liver

1971 ◽  
Vol 41 (2) ◽  
pp. 159-170 ◽  
Author(s):  
R. D. Cohen ◽  
R. A. Iles ◽  
D. Barnett ◽  
M. E. O. Howell ◽  
J. Strunin
Keyword(s):  
Intracellular Ph ◽  
Rat Liver ◽  
Liver Cell ◽  
Direct Relationship ◽  
Control Mechanism ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Lactate Uptake ◽  
Simultaneous Change

1. Mean intracellular pH (pHi) and lactate have been measured simultaneously in the isolated perfused rat liver on two successive occasions separated by an interval of 20 min. In some experiments extra lactate was added to the perfusion medium immediately after the first measurement of pHi. 2. There was a direct relationship between the change in pHi over this interval and the simultaneous change of lactate uptake. 3. This finding is consistent with the hypothesis that lactate enters the liver cell at least partly in the ionized form and that its metabolism is accompanied by the effective production of hydroxyl ions. 4. These observations are discussed in terms of a possible control mechanism for lactate uptake by the liver.

Effect of Hypothermia on the Hepatic Uptake and Biliary Excretion of Vecuronium in the Isolated Perfused Rat Liver

2001 ◽  
Vol 94 (2) ◽  
pp. 270-279 ◽  
Author(s):  
Ton M. Beaufort ◽  
Johannes H. Proost ◽  
Jan-Gerard Maring ◽  
Emiel R. Scheffer ◽  
J. Mark K. H. Wierda ◽  
...  
Keyword(s):  
Rat Liver ◽  
Biliary Excretion ◽  
Excretion Rate ◽  
Hepatic Uptake ◽  
Pharmacokinetic Analysis ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Perfusion Medium ◽  
Perfusion Experiment ◽  
Biliary Excretion Rate

Background Hypothermia prolongs the time course of action of nondepolarizing muscle relaxants. It is not known whether this prolongation is caused by a reduced rate of extrahepatic distribution or elimination, liver uptake, metabolic clearance, or biliary excretion. Therefore, the authors studied the effects of hypothermia on the net hepatic uptake, metabolism, and biliary excretion of vecuronium in isolated perfused rat liver. Methods Livers of Wistar rats were perfused with Krebs Ringer solution (1% albumin, 3.3% carbon dioxide in oxygen, pH 7.36-7.42, 38 degrees C). Each perfusion experiment (recirculatory perfusion system) was divided into three phases. In phase 1, a bolus dose of vecuronium (950 microg) was followed by a continuous infusion of vecuronium (63 microg/min) throughout the perfusion experiment. In phase 2, the temperature was reduced to 28 degrees C. In phase 3, temperature was restored. In controls, the temperature was kept constant throughout the perfusion. Concentrations of vecuronium and its metabolites were measured in perfusion medium, bile, and liver homogenate. Parameters of a multicompartmental liver model were fitted to the concentration patterns in perfusion medium and in bile. Results Hypothermia increased vecuronium concentrations in the perfusion medium from 4.0 microg/ml (range, 2.5-6.6) to 15.6 microg/ml (11.5-18.4 microg/ml; P = 0.018). Hypothermia reduced the biliary excretion rate of 3-desacetyl vecuronium from 18% (range, 6-37%) to 16% (range, 4-19%) of that of vecuronium (P = 0.018). Pharmacokinetic analysis confirmed that hypothermia reduced the rate constants of hepatic uptake and metabolism from 0.219 to 0.053 and from 0.059 to 0.030, respectively. Conclusions Hypothermia significantly and reversibly reduced the net hepatic uptake of vecuronium. Hypothermia reduced the metabolism of vecuronium and the biliary excretion rate of 3-desacetyl vecuronium.

A Comparison of Plasminogen Activators Derived from Rat Plasma, Primary Rat Hepatocytes and Isolated Perfused Rat Liver

1982 ◽  
Vol 47 (02) ◽  
pp. 166-172 ◽  
Author(s):  
Yoav Sharoni ◽  
Maria C Topal ◽  
Patricia R Tuttle ◽  
Henry Berger
Keyword(s):  
Rat Liver ◽  
Isoelectric Point ◽  
Rat Hepatocytes ◽  
Cell Types ◽  
Plasminogen Activators ◽  
Rat Plasma ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Molecular Weights ◽  
Physiological Relevance

SummaryOf the two cell types it was possible to culture from the dissociated rat liver, hepatocytes and Kupffer cells, only the former were fibrinolytically active. Rat hepatocytes during the first 24 hr in culture secreted two plasminogen activators with molecular weights identical to those found in rat plasma, an 80,000-dalton form (PA-80) and a 45,000-dalton form (PA-45). Partially purified preparations of plasminogen activators from both sources were subjected to isoelectric focusing (IEF) to compare characteristics further. There were three distinct peaks of PA-45 in each preparation with isoelectric points of 7.1, 7.2 and 7.4; all electrophoretic forms had the same low affinity to fibrin. PA-80 from both sources displayed similar IEF profiles with forms ranging from pH values of 7 to 8, all with the same high affinity to fibrin. The major form of PA-80 in the plasma preparation had an isoelectric point of 7.9 whereas that in the hepatocyte preparation had an isoelectric point of 7.6. The isolated perfused rat liver was also shown to produce both PA-80 and PA-45 emphasizing the physiological relevance of the findings with hepatocytes. It is concluded that in the rat hepatocytes contribute to the plasma profile with regard to the plasminogen activator content.

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