Reaction Phenotyping of Low-Turnover Compounds in Long-term Hepatocyte Cultures Through Persistent Selective Inhibition of Cytochromes P450

2021 ◽  
pp. DMD-AR-2021-000601
Author(s):  
Sheri R Smith ◽  
Michael J Lyman ◽  
Bennett Ma ◽  
Donald J Tweedie ◽  
Karsten Menzel
Keyword(s):  
Cytochromes P450 ◽  
Selective Inhibition ◽  
Hepatocyte Cultures ◽  
Reaction Phenotyping

INDUCTION AND INHIBITION OF CYTOCHROMES P450 BY THE ST. JOHN'S WORT CONSTITUENT HYPERFORIN IN HUMAN HEPATOCYTE CULTURES

2004 ◽  
Vol 32 (5) ◽  
pp. 512-518 ◽  
Author(s):  
Bernard J. Komoroski ◽  
Shimin Zhang ◽  
Hongbo Cai ◽  
J. Matthew Hutzler ◽  
Reginald Frye ◽  
...  
Keyword(s):  
Cytochromes P450 ◽  
Human Hepatocyte ◽  
St John’S Wort ◽  
Hepatocyte Cultures ◽  
St John's Wort

scholarly journals Lack of Small Intestinal Dysbiosis Following Long-Term Selective Inhibition of Cyclooxygenase-2 by Rofecoxib in the Rat

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 251 ◽  
Author(s):  
Bernadette Lázár ◽  
Gábor Brenner ◽  
András Makkos ◽  
Mihály Balogh ◽  
Szilvia László ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Mucosal Damage ◽  
Inhibitory Effect ◽  
Intestinal Dysbiosis ◽  
Bowel Diseases ◽  
Direct Inhibitory Effect ◽  
Cox 2 ◽  
Small Intestinal

Intestinal dysbiosis is linked to numerous gastrointestinal disorders, including inflammatory bowel diseases. It is a question of debate if coxibs, selective inhibitors of cyclooxygenase (COX)-2, cause dysbiosis. Therefore, in the present study, we aimed to determine the effect of long-term (four weeks) selective inhibition of COX-2 on the small intestinal microbiota in the rat. In order to avoid mucosal damage due to topical effects and inflammation-driven microbial alterations, rofecoxib, a nonacidic compound, was used. The direct inhibitory effect of rofecoxib on the growth of bacteria was ruled out in vitro. The mucosa-sparing effect of rofecoxib was confirmed by macroscopic and histological analysis, as well as by measuring the intestinal levels of cytokines and tight junction proteins. Deep sequencing of bacterial 16S rRNA revealed that chronic rofecoxib treatment had no significant influence on the composition and diversity of jejunal microbiota. In conclusion, this is the first demonstration that long-term selective inhibition of COX-2 by rofecoxib does not cause small intestinal dysbiosis in rats. Moreover, inhibition of COX-2 activity is not likely to be responsible per se for microbial alterations caused by some coxibs, but other drug-specific properties may contribute to it.

The use of Long-term Hepatocyte Cultures for Detecting Induction of Drug Metabolising Enzymes: The Current Status

1999 ◽  
Vol 27 (4) ◽  
pp. 579-638 ◽  
Author(s):  
Sandra Coecke ◽  
Vera Rogiers ◽  
Martin Bayliss ◽  
José Castell ◽  
Johannes Doehmer ◽  
...  
Keyword(s):  
Current Status ◽  
Hepatocyte Cultures ◽  
Drug Metabolising Enzymes

Collagen Gel Immobilisation Provides a Suitable Cell Matrix for Long Term Human Hepatocyte Cultures in Hybrid Reactors

1994 ◽  
Vol 17 (2) ◽  
pp. 95-106 ◽  
Author(s):  
H.G. Koebe ◽  
M. Wick ◽  
U. Cramer ◽  
V. Lange ◽  
F.W. Schildberg
Keyword(s):  
Human Hepatocyte ◽  
Hybrid Reactor ◽  
Artificial Organ ◽  
Total Production ◽  
Shear Forces ◽  
Culture Systems ◽  
Cell Functions ◽  
Hepatocyte Cultures ◽  
Hybrid Reactors

An easy to apply culture technique is presented that protects a monolayer configuration of liver cells within an extracellular matrix. The Immobilising Gel (IG)-Technique not only preserves hepatocyte morphology and supports a variety of differentiated cell functions over long term periods, but also offers higher resistance of IG-culture systems against shear forces of fluids in a hybrid reactor device, as compared to other culture techniques. Human hepatocyte cultures in IG-Technique: DNA-normalised levels for the total production of cholinesterase, albumin, urea and lactate remained high throughout the investigational period (50 days). Glutamic-Pyruvic-Transaminase (GPT) release decreased after peak values during early culture adaptation. Electron Microscopic (EM) findings after the shear forces experiment revealed undisturbed subcellular structures and a preserved intercellular morphology, including bile canaliculi and desmosomes. We conclude that the IG-technique is of considerable advantage as compared to other culture systems, especially in the field of dynamic applications, e.g. hybrid reactors for artificial organ development.

Application of Short- and Long-Term Hepatocyte Cultures to Predict Toxicities

2008 ◽  
pp. 139-174
Author(s):  
Gregor Tuschl ◽  
Jens Hrach ◽  
Philip G. Hewitt ◽  
Stefan O. Mueller
Keyword(s):  
Hepatocyte Cultures ◽  
Short And Long Term
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