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

1982 ◽  
Vol 100 (1) ◽  
pp. 57-62 ◽  
Author(s):  
M. Höller ◽  
H. Weber ◽  
H. Breuer
Keyword(s):  
Rat Liver ◽  
Glucuronic Acid ◽  
Small Extent ◽  
Isolated Rat Liver ◽  
Metabolic Reactions ◽  
Biliary Metabolite ◽  
Rat Livers ◽  
Isolated Rat

Abstract. Equimolar concentrations of [4-14C]oestriol and [6,9-3H2]oestriol 16α-monoglucuronide were simultaneously perfused through isolated rat livers. Oestriol was hydroxylated to 2-hydroxyoestriol and 6ξ-hydroxyoestriol; 2-hydroxyoestriol was further methylated to 2-methoxyoestriol. Oxidoreduction of oestriol led to the formation of 16α-hydroxyoestrone, 16-oxooestradiol-17β and 16-epioestriol. In addition, two dehydroxylation products, namely oestrone and oestradiol-17β were found. The metabolites formed from oestriol were partly conjugated to monoglucuronides, monosulphates and sulphoglucuronides. About 80% of the oestriol perfused was hydroxylated at C-atom 2. Most of the 2-hydroxyoestriol formed was either methylated (about 37%) or sulphated (about 55%). Only small amounts (less than 2%) of the catecholoestrogens formed were methylated as well as sulphated. The 2-hydroxyoestriol monosulphates accumulated in the liver. After their conjugation with glucuronic acid, the double conjugates formed were immediately excreted into the bile. In fact, 2-hydroxyoestriol 16α-monoglucuronide 2(3?)-monosulphate comprised by far the main biliary metabolite of [4-14C]oestriol, followed by oestriol 16α-monoglucuronide and 2-methoxyoestriol 16α-monoglucuronide. No tritiated sulphoglucuronides were detected, thus indicating that the monosulphates are the immediate precursors of the double conjugates. [6,9-3H2]Oestriol 16α-monoglucuronide was metabolised only to a small extent. After its uptake into the liver more than 90% of this conjugate was secreted unchanged into the bile. The remaining part was hydrolysed; the oestriol liberated followed the same metabolic reactions as those found for [4-14C]oestriol. This indicates that the 16α-glucuronide of oestriol is not metabolised to any appreciable extent.

scholarly journals Studies on the metabolism of oestrone sulphate. Comparative perfusions of oestrone and oestrone sulphate through isolated rat livers

1977 ◽  
Vol 166 (3) ◽  
pp. 363-371 ◽  
Author(s):  
Michael Höller ◽  
Wilhelm Grochtmann ◽  
Mechthild Napp ◽  
Heinz Breuer
Keyword(s):  
Liver Cell ◽  
Liver Tissue ◽  
Glucuronic Acid ◽  
First Passage ◽  
Large Reservoir ◽  
Isolated Rat Liver ◽  
Oestrone Sulphate ◽  
Rat Livers ◽  
Hydroxy Steroid ◽  
Isolated Rat

The metabolism of [4-14C]oestrone and of [6,7-3H2]oestrone sulphate was studied during cyclic perfusion and once-through perfusion of the isolated rat liver. The following results were obtained. 1. As shown by once-through perfusion, the two steroids are metabolized differently during the first passage through the organ. [4-14C]Oestrone was taken up by the liver and partly delivered as oestradiol-17β and oestriol into the medium. After uptake of [6,7-3H2]oestrone sulphate, only oestrone, liberated by hydrolysis, was delivered into the medium; no oestradiol-17β or oestriol could be detected in the medium after one passage through the organ. This indicates that intracellular oestrone, which was taken up as such, and oestrone, which derived from intracellular hydrolysis, may be metabolized in different compartments of the liver cell. 2. The results of the cyclic perfusion showed that intracellular oestrone is preferentially conjugated with glucuronic acid, and subsequently excreted into the bile. Intracellular oestrone sulphate is preferably reduced to oestradiol sulphate, thus indicating that oestrone sulphate is a better substrate for the 17β-hydroxy steroid oxidoreductase than is oestrone. 3. Albumin-bound oestrone sulphate acts as a large reservoir, and in contrast with free oestrone is protected from enzyme attack by its strong binding to albumin. 4. Oestrone sulphate is partly converted into the hormonally active oestrone by liver tissue. This suggests that liver not only inactivates oestrogens, but also provides the organism with oestrone, which is subsequently readily taken up by other organs.

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.

Ultrastructural changes in isolated rat liver perfused with cyclic heptapeptide toxins from norwegian freshwater cyanobacteria (blue-green algae)

1987 ◽  
Vol 45 ◽  
pp. 858-859
Author(s):  
A.S. Dabholkar ◽  
W.W. Carmichael ◽  
K. Berg ◽  
J. Wyman
Keyword(s):  
Ultrastructural Changes ◽  
Sprague Dawley ◽  
Isolated Rat Liver ◽  
Blue Green Algae ◽  
Sprague Dawley Rats ◽  
Cyclic Heptapeptide ◽  
Intracellular Changes ◽  
Oscillatoria Agardhii ◽  
Rat Livers ◽  
Isolated Rat

Intracellular changes in the hepatocytes of isolated rat livers perfused with cyclic heptapeptide toxins are described. The toxins used are 1) -Ala-Leu- β-methyl isoAsp-Arg-ADDA-isoGlu-mdha (M.W. 944) from Microcystis aeruginosa- Lake Akersvatn, Norway; 2) -Ala-Arg-isoAsp-Arg-ADDA-isoGlu-mdha (M.W. 1023) from Oscillatoria agardhii var. - Lake Kolbatnvatn, Norway; 3) -Ala-Arg-isoAsp-Arg-ADDA-isoGlu-dha (M.W. 1009) from Oscillatoria agardhii var. isothrix - Lake Froylandsvatn, Norway. Approximate LD intraperitoneal mouse for the toxins is 50, 500 and 1000 μg/kg respectively.Livers were removed from male Sprague Dawley rats and perfused for 15 min with a blood-free perfusate (50 ml) followed by 60 min with perfusate containing i) 25, 50, or 200 μg of M. aeruginosa toxin ii) 50, 250, 500 or 1000 μg of O. agardhii var. toxin and iii) 1000, 2000, 2500 or 5000 μg of O. agardhii var. isothrix toxin. Control livers were perfused for 75 min with the blood-free perfusate.

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