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.

Precision-cut Guinea-pig Liver Slices as a Tool for Studying the Toxicity of Volatile Anaesthetics

1990 ◽  
Vol 18 (1_part_1) ◽  
pp. 191-199
Author(s):  
Hanan N. Ghantous ◽  
Jeanne Fernando ◽  
Scott E. Morgan ◽  
A. Jay Gandolfi ◽  
Klaus Brandel
Keyword(s):  
Guinea Pig ◽  
Rank Order ◽  
Normal Liver ◽  
Liver Slice ◽  
Volatile Anaesthetics ◽  
Pig Liver ◽  
Liver Slices ◽  
Guinea Pig Liver ◽  
Krebs Henseleit Buffer

Cultured precision-cut liver slices retain normal liver architecture and physiological biochemical functions. Hartley male guinea-pig liver slices have proven to be a good model for studying the biotransformation and toxicity of halothane. This system was used to evaluate the biotransformation and toxicity of different volatile anaesthetics (halothane, enflurane, isoflurane and sevoflurane), and compare their effects to those of new anaesthetics (desflurane). Liver slices (250–300μm thick) were incubated in sealed roller vials, containing Krebs Henseleit buffer at 37°C under 95% O2:5% CO2 atmosphere. Volatile anaesthetics were delivered by volatilisation after pre-incubation for 1 hour to produce a constant concentration in the medium. Production of the metabolites, trifluroacetic acid and fluoride ion, was measured. Intracellular potassium ion content, protein synthesis and secretion were determined as indicators of viability of the slices. The rank order of biotransformation of anaesthetics by the liver slices was halothane >sevoflurane>isoflurane and enflurane>desflurane. The rank order of hepatotoxicity of these anaesthetics was halothane>isoflurane and enflurane>sevoflurane and desflurane. Halothane is the anaesthetic which is metabolised furthest and has the most toxic effect, while desflurane is the least metabolised anaesthetic and has the least toxicity. This in vitro cultured precision-cut liver slice system appears to be suitable for studying the biotransformation of volatile anaesthetics and correlating its role in the resulting toxicity.

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.

LPS-induced downregulation of MRP2 and BSEP in human liver is due to a posttranscriptional process

2004 ◽  
Vol 287 (5) ◽  
pp. G1008-G1016 ◽  
Author(s):  
Marieke G. L. Elferink ◽  
Peter Olinga ◽  
Annelies L. Draaisma ◽  
Marjolijn T. Merema ◽  
Klaas Nico Faber ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Rat Liver ◽  
Inducible Nitric Oxide Synthase ◽  
Human Liver ◽  
Mrna Levels ◽  
Liver Slices ◽  
Oxide Synthase ◽  
Human Liver Slices ◽  
Inducible Nitric Oxide

Endotoxin-induced cholestasis in rodents is caused by hepatic downregulation of transporters, including the basolateral Na+-dependent taurocholate transporter (ntcp) and the canalicular bile salt export pump (bsep) and multidrug resistance-associated protein 2 (mrp2). Details about the regulation of the human transporter proteins during this process are lacking. We used precision-cut human and rat liver slices to study the regulation of transporter expression during LPS-induced cholestasis. We investigated the effect of LPS on nitrate/nitrite and cytokine production in relation to the expression of inducible nitric oxide synthase, NTCP, BSEP, and MRP2 both at the level of mRNA with RT-PCR and protein using immunofluorescence microscopy. In liver slices from both species, LPS-induced expression of inducible nitric oxide synthase was detected within 1–3 h and remained increased over 24 h. In rat liver slices, this was accompanied by a significant decrease of rat ntcp and mrp2 mRNA levels, whereas bsep levels were not affected. These results are in line with previous in vivo studies and validate our liver slice technique. In LPS-treated human liver slices, NTCP mRNA was downregulated and showed an inverse correlation with the amounts of TNF-α and Il-1β produced. In contrast, MRP2 and BSEP mRNA levels were not affected under these conditions. However, after 24-h LPS challenge, both proteins were virtually absent in human liver slices, whereas marker proteins remained detectable. In conclusion, we show that posttranscriptional mechanisms play a more prominent role in LPS-induced regulation of human MRP2 and BSEP compared with the rat transporter proteins.

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

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 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

THE EFFECT OF FASTING ON ESTERIFICATION OF PALMITATE BY RAT LIVER IN VITRO

1966 ◽  
Vol 44 (1) ◽  
pp. 129-140 ◽  
Author(s):  
Bernard Rubenstein ◽  
David Rubinstein
Keyword(s):  
Rat Liver ◽  
Incubation Medium ◽  
Intact Cell ◽  
Glycerol Kinase ◽  
Glycerophosphate Dehydrogenase ◽  
Liver Slices ◽  
Liver Homogenates

The ability of liver slices from rats fasted 48 hours to esterify palmitate-1-14C is about half of that of slices from fed animals. The same effect can be observed in homogenates of liver freed of nuclei, either with or without mitochondria. In both preparations, the synthesis of triglycerides is chiefly affected. The decrease in esterification by homogenate supernatants containing microsomes from fasted animals can be overcome by using increased amounts of ATP or an ATP generator and NaF in the incubation medium. The ATPase responsible for the higher ATP requirement in liver homogenates from fasted animals is Mg++-dependent. Higher concentrations of ATP inhibit esterification by mitochondrial preparations. Incorporation of both palmitate-9-10-3H and of glycerol-1-3-14C is reduced to the same extent for each compound in slices from fasting animals. Glycerol kinase and α-glycerophosphate dehydrogenase are both unaffected by 48 hours' fasting. It is concluded that the decrease in ATP from the activation of ATPase is responsible for the decreased esterification in the intact cell.

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