Bioassay of endotoxin clearance in vivo and by perfused rat liver

1976 ◽  
Vol 231 (1) ◽  
pp. 258-264 ◽  
Author(s):  
BJ Buchanan ◽  
JP Filkins
Keyword(s):  
Linear Relationship ◽  
Rat Liver ◽  
Salt Solution ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Half Time ◽  
Rat Blood ◽  
Endotoxin Concentration ◽  
Induction Of Tolerance

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.

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.

Comparison of somatostatin-28 and somatostatin-14 clearance by the perfused rat liver

1985 ◽  
Vol 63 (1) ◽  
pp. 62-67 ◽  
Author(s):  
M. Seno ◽  
Y. Seino ◽  
Y. Takemura ◽  
S. Nishi ◽  
H. Ishida ◽  
...  
Keyword(s):  
Rat Liver ◽  
Gel Filtration ◽  
Perfused Rat Liver ◽  
Half Time ◽  
Hepatic Extraction Ratio ◽  
Plasma Extract ◽  
Second Peak ◽  
Somatostatin 14

The hepatic clearances of somatostatin (SS)-28 and SS-14 by the perfused rat liver were compared, using a recirculating, plasma-free, erythrocyte-containing perfusion system. The disappearance rate constant, half time, clearance, and hepatic extraction ratio when 1.2 nM SS-28 was added to the perfusate were 0.0221 ± 0.0051 min−1, 36.6 ± 7.6 min, 0.34 ± 0.08 mL/min, and 17.2 ± 3.9%, respectively. The corresponding values obtained when SS-14 was added to the perfusate were 0.0405 ± 0.0022 min−1, 17.3 ± 1.0 min, 0.71 ± 0.05 mL/min, and 35.4 ± 2.6%, respectively. The differences between the SS-28 and SS-14 indices were all statistically significant. In addition, the perfusates with SS-28 added were eluted on Sephadex G-25 fine columns and somatostatinlike immunoreactivity (SLI) was determined. No SS-14 was found in perfusate containing SS-28 at both 5 and 30 min after the beginning of the perfusion. To investigate whether or not the liver plays an important role in the clearance of SS-28 or the conversion of SS-28 to SS-14 in vivo, the plasma disappearance of 2 μg SS-28 was compared in the whole rat and the functionally hepatectomized model. The half time of plasma SS-28 was 1.43 ± 0.12 min in the whole rat, significantly shorter than the 2.20 ± 0.14 min in the hepatectomized model. Gel filtration of plasma extract samples at 0.5 min after the SS-28 injection showed two major peaks of SLI: a first peak corresponding to SS-28 and a second peak coeluted in the position of SS-14 in both the whole rat and the hepatectomized model. At 4 min after the SS-28 injection, the first peak disappeared and only a small second peak was observed. These results suggest that SS-28 is cleared by the rat liver in vivo and in vitro and that it is cleared more slowly than SS-14. Furthermore, we find that little, if any, conversion of SS-28 to SS-14 occurs in the liver.

Metabolic characteristics of the isolated perfused rat liver

1960 ◽  
Vol 199 (3) ◽  
pp. 395-399 ◽  
Author(s):  
Alvin S. Ostashever ◽  
Irving Gray ◽  
Samuel Graff
Keyword(s):  
Rat Liver ◽  
Amino Nitrogen ◽  
Experimental Period ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Metabolic Characteristics ◽  
Respiration Rates ◽  
Substrate Respiration ◽  
Body Production

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.

scholarly journals Metabolism of ornithine, α-ketoglutarate and arginine in isolated perfused rat liver

1995 ◽  
Vol 73 (2) ◽  
pp. 227-239 ◽  
Author(s):  
Jean Pascal De Bandt ◽  
Luc Cynober ◽  
Soo Kyung Lim ◽  
Colette Coudray-Lucas ◽  
Raoul Poupon ◽  
...  
Keyword(s):  
Rat Liver ◽  
Hepatic Metabolism ◽  
Isolated Perfused Rat Liver ◽  
Trauma Patients ◽  
Perfused Rat Liver ◽  
Metabolic Interaction ◽  
Urea Production ◽  
Stimulation Of

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.

T4 uptake into the perfused rat liver and liver T4 uptake in humans are inhibited by fructose

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 ◽  
...  
Keyword(s):  
Rat Liver ◽  
Human Subjects ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Before And After ◽  
Pool Model ◽  
Serum T4 ◽  
Uptake Process ◽  
Intracellular Energy

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.

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