THE METABOLISM OF ALDOSTERONE BY SURVIVING DOG AND HUMAN LIVER SLICES

1960 ◽  
Vol 38 (1) ◽  
pp. 739-756
Author(s):  
Thomas Sandor ◽  
Wojciech J. Nowaczynski ◽  
Jacques Genest
Keyword(s):  
Human Liver ◽  
Chemical Characterization ◽  
Liver Slices ◽  
Metabolic Products ◽  
Reducing Substances ◽  
Dog Liver ◽  
Human Liver Slices ◽  
Acetate Form

Surviving dog liver slices were incubated with d,l-aldosterone-21-monoacetate, d,l-aldosterone, d-aldosterone, and d-aldosterone-21-C14. Human liver slices were incubated with d,l-aldosterone-21-monoacetate and d-aldosterone. The incubations were performed in a Krebs–Ringer–phosphate medium (pH 7.4), with 200 mg glucose added per 100 ml of medium, at a temperature of 37 °C. After incubation, the medium was extracted with chloroform and the crude extract extensively fractionated on column and paper chromatographic systems. In addition to free aldosterone, four metabolic products were isolated, two ring A reduced α-ketolic and two ultraviolet absorbing, non-reducing substances. The partial chemical characterization of these metabolites was attempted. The search for aldosterone metabolites in human urine resulted in the isolation of a substance in acetate form from the urine of a patient suffering from primary aldosteronism which may be identical with one of the ring A reduced metabolites obtained in the in vitro experiments.

THE METABOLISM OF ALDOSTERONE BY SURVIVING DOG AND HUMAN LIVER SLICES

1960 ◽  
Vol 38 (7) ◽  
pp. 739-756 ◽  
Author(s):  
Thomas Sandor ◽  
Wojciech J. Nowaczynski ◽  
Jacques Genest
Keyword(s):  
Human Liver ◽  
Chemical Characterization ◽  
Liver Slices ◽  
Metabolic Products ◽  
Reducing Substances ◽  
Dog Liver ◽  
Human Liver Slices ◽  
Acetate Form

Surviving dog liver slices were incubated with d,l-aldosterone-21-monoacetate, d,l-aldosterone, d-aldosterone, and d-aldosterone-21-C14. Human liver slices were incubated with d,l-aldosterone-21-monoacetate and d-aldosterone. The incubations were performed in a Krebs–Ringer–phosphate medium (pH 7.4), with 200 mg glucose added per 100 ml of medium, at a temperature of 37 °C. After incubation, the medium was extracted with chloroform and the crude extract extensively fractionated on column and paper chromatographic systems. In addition to free aldosterone, four metabolic products were isolated, two ring A reduced α-ketolic and two ultraviolet absorbing, non-reducing substances. The partial chemical characterization of these metabolites was attempted. The search for aldosterone metabolites in human urine resulted in the isolation of a substance in acetate form from the urine of a patient suffering from primary aldosteronism which may be identical with one of the ring A reduced metabolites obtained in the in vitro experiments.

Metabolism of 16-Oxoœstrone by Human Liver Slices in vitro

Nature ◽  
1958 ◽  
Vol 182 (4648) ◽  
pp. 1512-1512 ◽  
Author(s):  
H. BREUER ◽  
R. KNUPPEN
Keyword(s):  
Human Liver ◽  
Liver Slices ◽  
Human Liver Slices

DNA Adduct Formation of Selected Sex Steroids in Human Liver Slices In Vitro

1998 ◽  
Vol 12 (4) ◽  
pp. 353-364 ◽  
Author(s):  
W. Feser ◽  
R.S. Kerdar ◽  
A. Baumann ◽  
J. Körber ◽  
H. Blode ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Human Liver ◽  
Adduct Formation ◽  
Dna Adduct ◽  
Liver Slices ◽  
Human Liver Slices

In- Vitro Hepatotoxicity of Three Dichlorobenzene Isomers in Human Liver Slices

1991 ◽  
Vol 10 (5) ◽  
pp. 357-363 ◽  
Author(s):  
Robyn Fisher ◽  
John Barr ◽  
Charles F. Zukoski ◽  
Charles W. Putnam ◽  
I. Glenn Sipes ◽  
...  
Keyword(s):  
Animal Models ◽  
Rat Liver ◽  
Incubation Medium ◽  
Human Liver ◽  
Rank Order ◽  
Liver Slices ◽  
Ultimate Question ◽  
Human Liver Slices ◽  
Krebs Henseleit Buffer

1 The cytotoxicity of dichlorobenzenes in cultured rat liver slices has previously been shown to be strain specific and biotransformation related. 2 In order to extrapolate animal models to humans, the dichlorobenzenes were incubated with human liver slices to try to clarify their hepatotoxic potential in man. 3 The degree of hepatotoxicity observed with the dichlorobenzenes depended on whether Waymouth's or Krebs-Henseleit was used as the incubation medium. 4 All three dichlorobenzenes (1 mM) produced no significant differences from control when incubated in Waymouth's medium. However, in the Krebs-Henseleit buffer there was a substantial increase in cytotoxicity. 5 In both incubation mediums the dichlorobenzene isomers exhibited the following rank order 1,3-DCB > 1,2-DCB > 1,4-DCB. 6 1,2-dichlorobenzene hepatotoxicity was blocked by metyrapone, 1,3-dichlorobenzene toxicity was blocked by SKF 525-A and neither one of these inhibitors could block the 1,4-dichlorobenzene cytotoxicity. 7 The use of human liver tissues to evaluate potential toxicants merits consideration since the hepatotoxicity of xenobiotics and drugs in man is the ultimate question.

Metabolism of Dimethylnitrosamine by Human Liver Slices in Vitro

Nature ◽  
1970 ◽  
Vol 228 (5267) ◽  
pp. 173-174 ◽  
Author(s):  
RUGGERO MONTESANO ◽  
P. N. MAGEE
Keyword(s):  
Human Liver ◽  
Liver Slices ◽  
Human Liver Slices

Comparative metabolism and toxicity of dichlorobenzenes in Sprague-Dawley, Fischer-344 and human liver slices

1995 ◽  
Vol 14 (5) ◽  
pp. 414-421 ◽  
Author(s):  
Robyn L Fisher ◽  
Steven J Hasal ◽  
I Glenn Sipes ◽  
A Jay Gandolfi ◽  
Klaus Brendel
Keyword(s):  
Metabolic Rate ◽  
Human Liver ◽  
Covalent Binding ◽  
Sprague Dawley ◽  
Fischer 344 ◽  
Liver Slices ◽  
Human Situation ◽  
Rat Strain ◽  
Human Liver Slices

1 Precision-cut liver slices, prepared from Sprague- Dawley and Fischer-344 rats and donated human liver tis sue, were used to identify differences in 1,2-dichloroben zene (1,2-DCB), 1,3-dichlorobenzene (1,3-DCB) and 1,4- dichlorobenzene (1,4-DCB) metabolism and how it may relate to toxicity. 2 Rat and human liver slices were incubated with 1 mM of either dichlorobenzene to determine metabolism and toxi city, at 2 and 6 h of organ culture. 3 The human liver slices metabolised the dichloroben zenes to a greater extent than those from either of the rat strains. Liver slices from the Fischer-344 strain had a higher metabolic rate than the slices from the Sprague- Dawley rat strain. 4 The metabolic rate of dichlorobenzene isomers did not consistently correlate with its toxicity. For example, human slices did not exhibit any hepatotoxicity, even though they metabolised these compounds to a greater extent than either rat strain. 5 Cross species covalent binding did not correlate with toxicity endpoints measured in this study. 6 The phase two metabolite profiles for each of the iso mers in human and rat slices were similar in that the glu tathione-cysteine conjugate was the major metabolite. 7 The use of an in vitro system which utilises human liver slices might provide an important bridge between animal derived data and the human situation.

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