THE METABOLISM OF ALDOSTERONE

1962 ◽  
Vol 39 (1) ◽  
pp. 87-102 ◽  
Author(s):  
Thomas Sandor ◽  
André Lanthier
Keyword(s):  
Human Kidney ◽  
Water Soluble ◽  
Tissue Slices ◽  
Kidney Slices ◽  
Liver Slices ◽  
Glucuronide Conjugation ◽  
The Media ◽  
Human Liver Slices ◽  
Acid Labile

ABSTRACT A study was made of the metabolism of synthetic dl- and d-aldosterone and biosynthetic d-aldosterone-4-14C by surviving human liver slices, and of the metabolism of d-aldosterone by human kidney slices. After incubation of aldosterone with the tissue slices in a Krebs-Ringer-phosphate glucose medium at 37° C, the media were subjected to fractional hydrolysis and extracted with chloroform. In this way, it was possible to study not only the metabolites of the substrate but also the formation of water soluble conjugates of these metabolites and of aldosterone. It was found that the major in vitro metabolite of aldosterone, using liver slices as a source of enzymes, was the glucuronide of a Ring A reduced α-ketolic steroid (A2). It was possible to show that this metabolite was identical to the tetrahydroaldosterone found in glucuronide conjugation in human urine. In addition, several other metabolites were isolated but in smaller quantities. These include metabolite A1, a possible stereoisomer of A2, two Δ4-3-ketonic, non reducing metabolites and a number of 14C substances characterized only by chromatographic mobilities. Chemically unchanged aldosterone was present in free, glucuronide and acid labile conjugation. Human kidney slices, in addition to producing small amounts of A2, did conjugate aldosterone in both the glucuronide and acid labile form. The intravenous infusion of d-aldosterone to an adrenalectomized patient resulted in the urinary excretion of A2-glucuronide, aldosterone-glucuronide and the mild acid labile aldosterone conjugate.

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.

scholarly journals In Vitro Effect of Crude Extract from Traganum Nudatum on Glucose-Uptake in Liver Slices Isolated from Westar Rats

2020 ◽  
Vol 4 (2) ◽  
pp. 550-551
Author(s):  
Faiza Mouderas
Keyword(s):  
Glucose Uptake ◽  
Crude Extract ◽  
Wistar Rats ◽  
Culture Media ◽  
Chronic Hyperglycemia ◽  
Liver Slices ◽  
Insulin Sensitizers ◽  
The Media ◽  
Vitro Effect

Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. There are many classes of drugs used for treatment, and these include insulin sensitizers, insulin secretagogues, and agents that delay the absorption of carbohydrates from the bowel. This study intends to investigate the effect of crude extract from a plant from South Algeria Traganum nudatum (Chenopodiaceae) on glucose uptake in liver slices isolated from Wistar rats. Methods: The liver slices were incubated for 90 min at 37° in normoglycaemic (1g/l of glucose) and hyperglycaemic (3g/l of glucose) KRBA Krebs Ringer Bicarbonate Albumin 4% media using 24 well-polyethylene plates. In each, well different concentrations of insulin (10, 50 and 100µU/ml) and hydromethanolic crude extract (100, 200 and 500µg/ml) were added. After every 30 minutes, aliquots of the culture media were assayed for the determination of glucose left. Results: Tests showed that the glucose left after 90 minutes in the media which contained insulin at 100µg/ml was the lowest (0.44 and 1.41 )g/l in the normo and hyperglycaemic media respectively, which reflect that insulin at this concentration was the most effective on the stimulation of glucose uptake. The extract had the highest effect at 500µg/ml, the concentrations of glucose left after 90 minutes of incubation were found to be (0.38 and 1.31)g/l in the normoglycaemic and hyperglycaemic media respectively. Conclusion: From the obtained results, it can be concluded that our extract seems to have an insulin-like effect on glucose uptake in liver slices isolated from Wistar rats.

NEGATIVE EFFECTS OF VITAMIN K PREPARATIONS ON GLUCURONYL TRANSFERASE ACTIVITY

PEDIATRICS ◽  
1967 ◽  
Vol 40 (6) ◽  
pp. 993-999
Author(s):  
Barbara Jones
Keyword(s):  
Vitamin K ◽  
Inhibitory Effect ◽  
Water Soluble ◽  
In Vivo Studies ◽  
Transferase Activity ◽  
Negative Effects ◽  
Glucuronyl Transferase ◽  
Glucuronide Conjugation

In vitro studies using a mouse liver microsome system failed to demonstrate that menadiol sodium diphosphate, menadione sodium bisulfite, or phytonadione enhanced or inhibited the quantity of ortho-aminophenol glucuronide produced. In vivo studies in young rats with these vitamin K analogues also failed to show an effect on glucuronide conjugation. Based on this data, it is concluded that the hyperbilirubinemia seen in prematures after large doses of water-soluble vitamin K analogues is probably not due to an inhibitory effect of glucuronyl transferase. The evidence suggesting that it may be due in part to hemolysis is briefly reviewed.

scholarly journals Progression of Repair and Injury in Human Liver Slices

2018 ◽  
Vol 19 (12) ◽  
pp. 4130
Author(s):  
Alison E.M. Vickers ◽  
Anatoly V. Ulyanov ◽  
Robyn L. Fisher
Keyword(s):  
Gene Expression ◽  
Human Liver ◽  
Wound Repair ◽  
Specific Gene ◽  
Drug Induced ◽  
Kidney Slices ◽  
Liver Slices ◽  
Liver And Kidney ◽  
Injury And Repair ◽  
Human Liver Slices

Human liver slice function was stressed by daily dosing of acetaminophen (APAP) or diclofenac (DCF) to investigate injury and repair. Initially, untreated human liver and kidney slices were evaluated with the global human U133A array to assess the extended culture conditions. Then, drug induced injury and signals of repair in human liver slices exposed to APAP or DCF (1 mM) were evaluated via specific gene expression arrays. In culture, the untreated human liver and kidney slices remained differentiated and gene expression indicated that repair pathways were activated in both tissues. Morphologically the human liver slices exhibited evidence of repair and regeneration, while kidney slices did not. APAP and DCF exposure caused a direct multi-factorial response. APAP and DCF induced gene expression changes in transporters, oxidative stress and mitochondria energy. DCF caused a greater effect on heat shock and endoplasmic reticulum (ER) stress gene expression. Concerning wound repair, APAP caused a mild repression of gene expression; DCF suppressed the expression of matrix collagen genes, the remodeling metalloproteases, cell adhesion integrins, indicating a greater hinderance to wound repair than APAP. Thus, human liver slices are a relevant model to investigate the mechanisms of drug-induced injury and repair.

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

scholarly journals Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Emiko Mihara ◽  
Hidenori Hirai ◽  
Hideki Yamamoto ◽  
Keiko Tamura-Kawakami ◽  
Mami Matano ◽  
...  
Keyword(s):  
Cellular Systems ◽  
Water Soluble ◽  
Biologically Active ◽  
Soluble Form ◽  
Wnt Ligands ◽  
Growth Assay ◽  
The Media ◽  
Highly Hydrophobic

Wnt plays important role during development and in various diseases. Because Wnts are lipidated and highly hydrophobic, they can only be purified in the presence of detergents, limiting their use in various in vitro and in vivo assays. We purified N-terminally tagged recombinant Wnt3a secreted from cells and accidentally discovered that Wnt3a co-purified with a glycoprotein afamin derived from the bovine serum included in the media. Wnt3a forms a 1:1 complex with afamin, which remains soluble in aqueous buffer after isolation, and can induce signaling in various cellular systems including the intestical stem cell growth assay. By co-expressing with afamin, biologically active afamin-Wnt complex can be easily obtained in large quantity. As afamin can also solubilize Wnt5a, Wnt3, and many more Wnt subtypes, afamin complexation will open a way to put various Wnt ligands and their signaling mechanisms under a thorough biochemical scrutiny that had been difficult for years.

The effect of ammonium on photosynthesis and the pathway of ammonium assimilation in Gymnodinium microadriaticum in vitro and in symbiosis with tridacnid clams and corals

1986 ◽  
Vol 227 (1247) ◽  
pp. 147-159 ◽  
Keyword(s):  
Amino Acids ◽  
Ammonium Assimilation ◽  
Water Soluble ◽  
Ammonium Uptake ◽  
Ammonium Ion ◽  
Ammonium Ions ◽  
Tissue Slices ◽  
Marine Animals ◽  
Symbiotic Algae

The effects of added ammonium ion (10-1000 μM) on photosynthetic 14 CO 2 fixation by tissues slices from the mantle of tridacnid clams, by coral tips, and by isolated zooxanthellae from clam mantle were examined. Ammonium ions stimulated photosynthesis in tissue slices but not in freshly isolated zooxanthellae. When ammonium stimulated 14 CO 2 fixation by coral tips an increase in water-soluble labelled compounds, especially amino acids, was observed. Even though ammonium ions did not stimulate photosynthesis in isolated zooxanthellae from clam mantle, light stimulated ammonium uptake in these cells. Studies with 15 NH + 4 confirmed earlier observations (in zooxanthellae isolated from Hippopus ) of light-stimulated transfer of ammonium from the amido-N of glutamine to the amino-N of glutamate, glutamine and other amino acids. This observation, in isolated zooxanthellae and tissue slices, suggests that the glutamine synthase-glutamate synthetase pathway of ammonium incorporation is light-driven in these systems. The possible significance of these processes during ammonium recycling by symbiotic algae in marine animals is discussed.

Toxicity of Cisplatin and Mercuric Chloride in Human Kidney Cortical Slices

1994 ◽  
Vol 13 (8) ◽  
pp. 517-523 ◽  
Author(s):  
Robyn L. Fisher ◽  
Jeffery T. Sanuik ◽  
A. Jay Gandolfi ◽  
Klaus Brendel
Keyword(s):  
Mercuric Chloride ◽  
Human Kidney ◽  
Time Dependent ◽  
Toxic Response ◽  
In Vitro System ◽  
Kidney Slices ◽  
Organ Specific ◽  
Cortical Slices

1 Organ specific toxicity such as nephrotoxicity is often investigated with the use of in vivo or in vitro animal models. 2 It would be beneficial if these findings could be verified in a human in vitro system which utilizes non-transplantable human kidneys. 3 Non-transplantable human kidneys were decapsulated, cut in half along the long axis, cores made perpendicular to the hemisphere, and precision-cut renal cortical slices produced. 4 These human kidney slices were incubated for 3, 6, 12, 18 and 24 h, viability assessed using intracellular K+ content, protein synthesis and organic ion transport and the potential nephrotoxicity of cisplatin (0.25, 0.5 and 1.0 mM) and mercuric chloride (10, 50 and 100 μm) on these slices were examined. 5 Control human kidney slices were viable for up to 24 h using all viability parameters while a dose-and time-dependent toxic response was seen using both cisplatin and mercuric chloride. 6 Cisplatin was more nephrotoxic in this human in vitro system than in previously investigated in vitro animal systems whereas mercuric chloride was similar in both systems. 7 These results indicate that human renal cortical slices are useful in predicting and verifying potentially nephrotoxic compounds in man.

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