Quantitative Time-Lapse Imaging-Based Analysis of Drug-Drug Interaction Mediated by Hepatobiliary Transporter, Multidrug Resistance-Associated Protein 2, in Sandwich-Cultured Rat Hepatocytes

2011 ◽  
Vol 39 (6) ◽  
pp. 984-991 ◽  
Author(s):  
Takeo Nakanishi ◽  
Yuta Shibue ◽  
Yoko Fukuyama ◽  
Kenji Yoshida ◽  
Hajime Fukuda ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Multidrug Resistance ◽  
Rat Hepatocytes ◽  
Time Lapse ◽  
Cultured Rat Hepatocytes ◽  
Drug Drug Interaction ◽  
Time Lapse Imaging

Application of quantitative time-lapse imaging (QTLI) for evaluation of Mrp2-based drug–drug interaction induced by liver metabolites

2012 ◽  
Vol 263 (2) ◽  
pp. 244-250 ◽  
Author(s):  
Takeo Nakanishi ◽  
Miho Ikenaga ◽  
Hajime Fukuda ◽  
Norikazu Matsunaga ◽  
Ikumi Tamai
Keyword(s):  
Drug Interaction ◽  
Time Lapse ◽  
Drug Drug Interaction ◽  
Time Lapse Imaging

Electron microscopic and time lapse studies of mitosis in cultured rat hepatocytes

Hepatology ◽  
1988 ◽  
Vol 8 (6) ◽  
pp. 1540-1549 ◽  
Author(s):  
Carol A. Sattler ◽  
Norimasa Sawada ◽  
Gerald L. Sattler ◽  
Henry C. Pitot
Keyword(s):  
Rat Hepatocytes ◽  
Time Lapse ◽  
Electron Microscopic ◽  
Cultured Rat Hepatocytes

scholarly journals Mature rat hepatocyte dedifferentiation into long lived proliferating hepatic progenitor cells

2021 ◽  
Vol 23 (3) ◽  
pp. 148-161
Author(s):  
A. M. Grigoriev ◽  
I. V. Kholodenko ◽  
A. Y. Lupatov ◽  
R. V. Kholodenko ◽  
L. A. Kirsanova ◽  
...  
Keyword(s):  
Small Molecules ◽  
Progenitor Cells ◽  
Wnt Signaling Pathway ◽  
Morphological Characteristics ◽  
Rat Hepatocytes ◽  
Time Lapse ◽  
Culture Cell ◽  
Proliferating Cells ◽  
Time Lapse Imaging ◽  
Growth Features

Objective: to obtain long-lived proliferating cells with progenitor features by dedifferentiation of mature rat hepatocytes using combinations of small molecules.Materials and Methods. Hepatocytes isolated from rat liver by perfusion were cultured in the presence of a cocktail of three small molecules – Wnt signaling pathway activator (CHIR99021), TGF-β inhibitors (A83-01) and ROCK kinase (Y27632). The morphological characteristics and growth features of the culture were assessed using fluorescence and phase-contrast microscopy during cell culture. Cell proliferative activity was analyzed using real-time time-lapse imaging. The expression of surface and intracellular markers was analyzed using flow cytometry and high-resolution fluorescence microscopy.Results. Using a cocktail of small molecules, Y-27632, A-83-01, and CHIR99021, long-lived proliferating cells that express progenitor cell markers, such as α-fetoprotein and HNF4α, were obtained from mature rat hepatocytes. The cells had hepatocyte-like morphology and formed discrete clusters of proliferating cells, forming a single cell layer during culturing. Removal of the small molecules from the medium led to expansion of fibroblast-like cells and elimination of potentially progenitor hepatocyte-like cells.Conclusion. Proliferating progenitor cells can be obtained by dedifferentiation of mature hepatocytes.

In vitro modulation of the cytochrome P450 and ABCB1/P-glycoprotein activities of the aqueous extract of Allophylus cominia (L) Sw. leaves

2017 ◽  
Vol 32 (4) ◽  
Author(s):  
Carlos L. Pérez ◽  
Maria T. Donato ◽  
Ivones Hernández ◽  
Miriam T. Paz Lopes ◽  
Evangelina Marrero ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Cell Viability ◽  
Aqueous Extract ◽  
Rat Hepatocytes ◽  
Mtt Test ◽  
P Glycoprotein ◽  
Cultured Rat Hepatocytes ◽  
Cyp 1A2

AbstractBackground:The aqueous extract of theMethods:Considering the herb–drug interaction, the aim of this study was to evaluate the potential effects of theResults:The extract did not decrease the cell viability after being assayed by the MTT test at up to 1500 μg/mL for 72 h. The exposure of the cultured rat hepatocytes to the product (up to 250 μg/mL) for 48 h increased the activities of CYP-1A2, 2C9, and 2E1 by 1.46-, 1.60-, and 1.51-fold, respectively, compared with the controls. The activities of CYP-2B6, 2D6, and 3A4 were not significantly altered, whereas the activity of P-gp decreased by 2- and 4-fold. In addition, the extracts at 100 and 200 μg/mL significantly increased doxorubicin cytotoxicity in these cells 24 h after treatment.Conclusions:The findings indicate that the

scholarly journals Dexamethasone- and osmolarity-dependent expression of the multidrug-resistance protein 2 in cultured rat hepatocytes1

1999 ◽  
Vol 340 (3) ◽  
pp. 585-591 ◽  
Author(s):  
Ralf KUBITZ ◽  
Ulrich WARSKULAT ◽  
Marcus SCHMITT ◽  
Dieter HÄUSSINGER
Keyword(s):  
Multidrug Resistance ◽  
Culture Medium ◽  
Rat Hepatocytes ◽  
Multidrug Resistance Protein ◽  
Short Term ◽  
Multidrug Resistance Protein 2 ◽  
Long Term Effect ◽  
Cultured Rat Hepatocytes ◽  
Resistance Protein

Expression of the conjugate export pump multidrug-resistance protein 2 (MRP2) in liver is regulated by endotoxin and anti-tumour agents. This paper reports on the effects of dexamethasone and osmolarity on MRP2 expression. MRP2 expression was studied at the protein, mRNA, immunocytochemical and functional levels in cultured rat hepatocytes. Protein and mRNA expression of MRP2 in rat hepatocytes 24 and 48 h after isolation were largely dependent on the presence of dexamethasone (100 nmol/l) in the culture medium. MRP2 was localized at the pseudocanalicular membrane and increased expression of MRP2 was accompanied by a widening of the pseudocanaliculi. In presence of dexamethasone, hypo-osmolarity (205 mosmol/l) led to a strong induction of MRP2 mRNA and protein, whereas expression was decreased by hyperosmolarity (405 mosmol/l). Also, a decay of MRP2 protein and mRNA following dexamethasone withdrawal was osmosensitive. Expression of dipeptidylpeptidase IV, another canalicular protein, was unaffected by dexamethasone and osmolarity. It is concluded that glucocorticoids are strong inducers of MRP2 in liver. Besides short-term carrier insertion/retrieval, osmoregulation of MRP2 also involves a long-term effect on MRP2 expression.

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