scholarly journals Primary Human Hepatocytes, But not HepG2 or Balb/c 3T3 Cells, Efficiently Metabolize Salinomycin and Are Resistant to Its Cytotoxicity

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1174
Author(s):  
Lidia Radko ◽  
Małgorzata Olejnik ◽  
Andrzej Posyniak
Keyword(s):  
Pharmacokinetic Interaction ◽  
Fibroblast Cell ◽  
Cell Types ◽  
Mouse Fibroblast ◽  
Human Hepatocytes ◽  
3T3 Cells ◽  
Primary Hepatocytes ◽  
Human Hepatoma Cells ◽  
Mouse Fibroblast Cell Line ◽  
Human Primary Hepatocytes

Salinomycin is a polyether antibiotic showing anticancer activity. There are many reports of its toxicity to animals but little is known about the potential adverse effects in humans. The action of the drug may be connected to its metabolism. That is why we investigated the cytotoxicity of salinomycin and pathways of its biotransformation using human primary hepatocytes, human hepatoma cells (HepG2), and the mouse fibroblast cell line (Balb/c 3T3). The cytotoxicity of salinomycin was time-dependent, concentration-dependent, and cell-dependent with primary hepatocytes being the most resistant. Among the studied models, primary hepatocytes were the only ones to efficiently metabolize salinomycin but even they were saturated at higher concentrations. The main route of biotransformation was monooxygenation leading to the formation of monohydroxysalinomycin, dihydroxysalinomycin, and trihydroxysalinomycin. Tiamulin, which is a known inhibitor of CYP450 izoenzymes, synergistically induced cytotoxicity of salinomycin in all cell types, including non-metabolising fibroblasts. Therefore, the pharmacokinetic interaction cannot fully explain tiamulin impact on salinomycin toxicity.

scholarly journals General Strategy for Broadening Adenovirus Tropism

2003 ◽  
Vol 77 (20) ◽  
pp. 11094-11104 ◽  
Author(s):  
Laura Fontana ◽  
Maurizio Nuzzo ◽  
Lorena Urbanelli ◽  
Paolo Monaci
Keyword(s):  
Fibroblast Cell ◽  
Adenovirus Type ◽  
Cell Types ◽  
Mouse Fibroblast ◽  
Broad Host Range ◽  
General Strategy ◽  
Immature Dendritic Cells ◽  
Mouse Fibroblast Cell Line ◽  
Adenovirus Receptor ◽  
Nih 3T3

ABSTRACT In spite of its broad host range, adenovirus type 5 (Ad5) transduces a number of clinically relevant tissues and cell types inefficiently, mostly because of low expression of the coxsackievirus-adenovirus receptor (CAR). To improve gene transfer to such cells, we modified the Ad5 fiber knob to recognize novel receptors. We expressed a functional Ad5 fiber knob domain on the capsid of phage λ and employed this display system to construct a large collection of ligands in the HI loop of the Ad5 knob. Panning this library on the CAR-negative mouse fibroblast cell line NIH 3T3 resulted in the identification of three clones with increased binding to these cells. Adenoviruses incorporating these ligands in the fiber gene transduced NIH 3T3 cells 2 or 3 orders of magnitude better than the parent vector. The same nonnative tropism was revealed in other cell types, independently of CAR expression. These Ad5 derivatives proved capable of transducing mouse and human primary immature dendritic cells with up to 100-fold increased efficiency.

Rosette formation by a mouse fibroblast cell line

Nature ◽  
1974 ◽  
Vol 248 (5448) ◽  
pp. 514-515 ◽  
Author(s):  
E. V. ELLIOTT ◽  
R. S. KERBEL ◽  
B. J. PHILLIPS
Keyword(s):  
Cell Line ◽  
Fibroblast Cell ◽  
Mouse Fibroblast ◽  
Rosette Formation ◽  
Fibroblast Cell Line ◽  
Mouse Fibroblast Cell ◽  
Mouse Fibroblast Cell Line

Sodium affinity of brain Na(+)-K(+)-ATPase is dependent on isozyme and environment of the pump

1990 ◽  
Vol 258 (5) ◽  
pp. C803-C811 ◽  
Author(s):  
J. L. Brodsky ◽  
G. Guidotti
Keyword(s):  
Plasma Membranes ◽  
Fibroblast Cell ◽  
Mouse Fibroblast ◽  
Synaptic Plasma Membranes ◽  
Apparent Dissociation Constant ◽  
Low Sodium ◽  
Physiological Relevance ◽  
Mouse Fibroblast Cell Line

The sodium affinities for the two forms of the Na(+)-K(+)-ATPase in brain were characterized. To mimic physiological conditions, synaptosomes, which are pinched off presynaptic nerve termini, were used. Examination of the pump in vitro was performed by preparing synaptic plasma membranes (SPMs). It was first shown that synaptosomes contain the two forms of the Na(+)-K(+)-ATPase, alpha 1 and alpha 2, and that these forms have markedly different affinities for the inhibitory cardiac glycoside ouabain. The apparent dissociation constant (K0.5) of alpha 1 for sodium changed from 12 to 9 mM when going from synaptosomes to membranes. For alpha 2, however, a shift from 36 to 12.5 mM was evident. The conclusion is that in vivo alpha 2 exists as a low sodium affinity species but can be altered to a high-affinity form simply by vesicle disruption. By comparison, the Na(+)-K(+)-ATPase from the mouse fibroblast cell line, 3T3-F442A cells, expressed only the alpha 1-isozyme, as shown by immunoblotting and by measurement of its ouabain and sodium affinities. The physiological relevance of these observations is also presented.

scholarly journals Evaluation of cytotoxicity of 5-n-alkylresorcinol homologs and fraction on mouse fibroblast cell line L929

2016 ◽  
Vol 243 (7) ◽  
pp. 1137-1148 ◽  
Author(s):  
Izabela Biskup ◽  
Ewa Zaczynska ◽  
Miroslawa Krauze-Baranowska ◽  
Izabela Fecka
Keyword(s):  
Cell Line ◽  
Fibroblast Cell ◽  
Mouse Fibroblast ◽  
Fibroblast Cell Line ◽  
Mouse Fibroblast Cell ◽  
Mouse Fibroblast Cell Line

scholarly journals Development of Bionanocomposites Based on PLA, Collagen and AgNPs and Characterization of Their Stability and In Vitro Biocompatibility

2020 ◽  
Vol 10 (7) ◽  
pp. 2265
Author(s):  
Maria Râpă ◽  
Laura Mihaela Stefan ◽  
Traian Zaharescu ◽  
Ana-Maria Seciu ◽  
Anca Andreea Țurcanu ◽  
...  
Keyword(s):  
Normal Growth ◽  
Fibroblast Cell ◽  
Stability Study ◽  
Mouse Fibroblast ◽  
Poly Lactic Acid ◽  
In Vitro Biocompatibility ◽  
Diphenyltetrazolium Bromide ◽  
Mouse Fibroblast Cell Line ◽  
The Stability

Bionanocomposites including poly(lactic acid) (PLA), collagen, and silver nanoparticles (AgNPs) were prepared as biocompatible and stable films. Thermal properties of the PLA-based bionanocomposites indicated an increase in the crystallinity of PLA plasticized due to a small quantity of AgNPs. The results on the stability study indicate the promising contribution of the AgNPs on the durability of PLA-based bionanocomposites. In vitro biocompatibility conducted on the mouse fibroblast cell line NCTC, clone 929, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed high values of cell viability (>80%) after cell cultivation in the presence of bionanocomposite formulations for 48 h, while the percentages of lactate dehydrogenase (LDH) released in the culture medium were reduced (<15%), indicating no damages of the cell membranes. In addition, cell cycle analysis assessed by flow cytometry indicated that all tested bionanocomposites did not affect cell proliferation and maintained the normal growth rate of cells. The obtained results recommend the potential use of PLA-based bionanocomposites for biomedical coatings.

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