Aging in vivo and neuraminidase treatment of rat erythrocytes and their sequestration by the isolated perfused rat liver

1985 ◽  
Vol 4 (2) ◽  
pp. 125-132 ◽  
Author(s):  
Thomas Vömel ◽  
Klaus Hager ◽  
Dieter Platt
1978 ◽  
Vol 176 (3) ◽  
pp. 959-965 ◽  
Author(s):  
Gerard J. Mulder ◽  
Katja Keulemans

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.


1976 ◽  
Vol 231 (1) ◽  
pp. 258-264 ◽  
Author(s):  
BJ Buchanan ◽  
JP Filkins

Endotoxin clearances in vivo and by the isolated perfused rat liver were evaluated via bioassay in lead-sensitized rats. A linear relationship between the probit of shock lethality and the endotoxin dose in the probit range of 4-6 was validated. Endotoxin clearance in normal, fed rats displayed a linear relationship between the logarithm of the blood endotoxin concentration and time throughout the period of 15-240 min at doses of 500 and 1,000 mug/ rat; the half-time values were 58-63 min. Decreasing the endotoxin dose to 250 mug resulted in multiphasic clearance curves. Induction of tolerance to endotoxin resulted in marked acceleration of endotoxin clearance. Endotoxin clearance from the isolated perfused rat liver was not influenced by serum or rat blood as compared to clearance from a balanced salt solution. These data suggest that a physiologically stressful dose of endotoxin is slowly cleared from the blood and, therefore, circulates for prolonged periods.


1960 ◽  
Vol 199 (3) ◽  
pp. 395-399 ◽  
Author(s):  
Alvin S. Ostashever ◽  
Irving Gray ◽  
Samuel Graff

The use of the isolated perfused rat liver for quantitative biochemical studies of liver metabolism over an experimental period of as long as 4 hours is demonstrated. Respiration rates responded immediately to the addition of substrates and the liver could be restimulated by a second dose of substrate, respiration rates reflecting the nature of the substrate. Net amino nitrogen uptake was consistently exceeded by urea nitrogen production, the latter comparing favorably with in vivo rates. Fructose was rapidly removed from the perfusate by the liver, and the liver efficiently removed lactic acid formed by erythrocyte glycolysis. Ketone body production was continuous and within normal in vivo rates. Bile production declined gradually over a 4-hour period.


1995 ◽  
Vol 73 (2) ◽  
pp. 227-239 ◽  
Author(s):  
Jean Pascal De Bandt ◽  
Luc Cynober ◽  
Soo Kyung Lim ◽  
Colette Coudray-Lucas ◽  
Raoul Poupon ◽  
...  

Ornithine (Orn; α-ketoglutarate (αKG) salt) and arginine (Arg) supplementation of enteral diets has been advocated in the treatment of hypercatabolism of trauma patients, but both compounds are subject to extensive hepatic metabolism. To compare the metabolism of these two compounds and to evaluate the possible influence of the αKG moiety, livers were perfused with αKG, Orn, ornithine α-ketoglutarate (OKG) or Arg (n 6 in each group) for 1 h. Arg uptake was nearly fourfold higher than Orn uptake (690 (SD 162) ν. 178 (SD 30) nmol/min per g liver), and Orn uptake was not modified by αKG. Orn was totally metabolized by the liver, whereas Arg led to Orn release (408 (SD 159) nmol/min per g liver) and a threefold stimulation of urea production (Arg 1·44 (SD 0·22) ν. Orn 0·45 (SD 0.09) μol/min per g liver). αKG alone only increased hepatic aspartate uptake but, when associated with Orn as OKG, it led to an increase in giutamate release and in proiine content in the liver and to a decrease in proiine uptake. From these findings we conclude that (1) Arg load is extensively metabolized by the liver, inducing urea production, (2) in enteral use, Orn supplementation appears preferable to Arg as it is less ureogenic (as also recently demonstrated in vivo in stressed rats receiving isomolar amounts of Arg and Orn), (3) the liver participates in the Orn-αKG metabolic interaction, mostly in proiine metabolism, which occurs in the splanchnic area.


1994 ◽  
Vol 266 (5) ◽  
pp. E768-E775 ◽  
Author(s):  
M. De Jong ◽  
R. Docter ◽  
B. F. Bernard ◽  
J. T. van der Heijden ◽  
H. van Toor ◽  
...  

Recently, we described a two-pool model for 3,5,3'-triiodothyronine uptake and metabolism in the isolated perfused rat liver. Here, we applied this model to investigate transmembrane thyroxine (T4) transport and its possible ATP dependence in vivo. These studies are performed in perfused rat livers during perfusion with or without fructose in the medium, as it has been shown that intracellular ATP is decreased after fructose loading. Furthermore, we studied serum T4 tracer disappearance curves in four human subjects before and after intravenous fructose loading. In the perfused rat liver, we found a decrease in liver ATP concentration and a decrease in medium T4 disappearance and T4 uptake in the liver pool after fructose. Furthermore, it was shown that, when corrected for differences in the medium free hormone concentration, only transport to the metabolizing liver pool was decreased after fructose perfusion, whereas uptake in the nonmetabolizing pool was unaffected. Disposal, corrected for differences in transport into the metabolizing pool, was also not affected after fructose. In the human studies, intravenous fructose administration induced a rise in serum lactic acid and uric acid, indicating a decrease in liver ATP. This was observed concomitant with a decrease in serum tracer T4 disappearance during the first 3 h after fructose administration. These results suggest ATP dependence of transport of iodothyronines into the liver in vivo and show that, in the rat liver and in humans, uptake of T4 may be regulated by intracellular energy stores; in this way the tissue uptake process may affect intracellular metabolism and bioavailability of thyroid hormone.


1958 ◽  
Vol 192 (3) ◽  
pp. 531-537 ◽  
Author(s):  
Alan M. Thompson ◽  
H. Mead Cavert ◽  
Nathan Lifson

Isolated rat livers were perfused via the portal vein with a blood-Ringer mixture containing a constant inflow concentration of D2O and, in some cases, antipyrine. The rate of increase of outflow concentration was studied, comparisons being made between D2O, antipyrine and a theoretical outflow curve based on completely flow-limited distribution. The effect of flow rate on the deviation of D2O from theoretical was also studied. The results indicate that exchange of D2O and antipyrine between blood and tissue in the perfused rat liver is extremely rapid relative to the rate of blood supply of these substances to the organ, even at flows several times that occurring in vivo. In the average experiment the average D2O concentration in the liver during the early period of the perfusion was about 90% of the mixed venous concentration. The factors responsible for the failure of D2O to distribute maximally, particularly tissue perfusion heterogeneity and diffusion limitation, are discussed. Although quantitation of the difference is difficult, antipyrine appears to distribute somewhat more rapidly than D2O due to its greater solubility in cell membranes.


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