scholarly journals Inhibitory Effect of Flavonoids on the Efflux of -Acetyl 5-Aminosalicylic Acid Intracellularly Formed in Caco-2 Cells

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Shin Yoshimura ◽  
Kentaro Kawano ◽  
Ryusuke Matsumura ◽  
Narumi Sugihara ◽  
Koji Furuno
Keyword(s):  
Tissue Culture ◽  
Cyclosporin A ◽  
Inhibitory Effect ◽  
Aminosalicylic Acid ◽  
Promoting Effect ◽  
Cellular Accumulation ◽  
P Glycoprotein ◽  
Apical Site ◽  
Apical Membranes ◽  
Glycoprotein Inhibitors

-acetyl 5-aminosalicylic acid (5-AcASA) that was intracellularly formed from 5-aminosalicylic acid (5-ASA) at 200 M was discharged 5.3, 7.1, and 8.1-fold higher into the apical site than into the basolateral site during 1, 2, and 4-hour incubations, respectively, in Caco-2 cells grown in Transwells. The addition of flavonols (100 M) such as fisetin and quercetin with 5-ASA remarkably decreased the apically directed efflux of 5-AcASA. When 5-ASA (200 M) was added to Caco-2 cells grown in tissue culture dishes, the formation of 5-AcASA decreased, and, in addition, the formed 5-AcASA was found to be accumulated within the cells in the presence of such flavonols. Thus, the decrease in 5-AcASA efflux by such flavonols was attributed not only to the inhibition of -acetyl-conjugation of 5-ASA but to the predominant cellular accumulation of 5-AcASA. Various flavonoids also had both of the effects with potencies that depend on their specific structures. The essential structure of flavonoids was an absence of a hydroxyl substitution at the C5 position on the A-ring of flavone structure for the inhibitory effect on the -acetyl-conjugation of 5-ASA, and a presence of hydroxyl substitutions at the C or C position on the B-ring of flavone structure for the promoting effect on the cellular accumulation of 5-AcASA. Both the decrease in 5-AcASA apical efflux and the increase in 5-AcASA cellular accumulation were also caused by MK571 and indomethacin, inhibitors of MRPs, but not by quinidine, cyclosporin A, P-glycoprotein inhibitors, and mitoxantrone, a BCRP substrate. These results suggest that certain flavonoids suppress the apical efflux of 5-AcASA possibly by inhibiting MRPs pumps located on apical membranes in Caco-2 cells.

Inhibitory effect of cyclosporin A on p-Glycoprotein function in peripheral nerves of mice treated with doxorubicin and vinblastine

2004 ◽  
Vol 124 (3) ◽  
pp. 313-317 ◽  
Author(s):  
Takehisa Saito ◽  
Zhi-Jian Zhang ◽  
Toshio Ohtsubo ◽  
Ichiro Noda ◽  
Masaharu Tokuriki ◽  
...  
Keyword(s):  
Cyclosporin A ◽  
Peripheral Nerves ◽  
Inhibitory Effect ◽  
P Glycoprotein

scholarly journals Comparative Study of the Effects of Antituberculosis Drugs and Antiretroviral Drugs on Cytochrome P450 3A4 and P-Glycoprotein

2014 ◽  
Vol 58 (6) ◽  
pp. 3168-3176 ◽  
Author(s):  
Yasuhiro Horita ◽  
Norio Doi
Keyword(s):  
Cytochrome P450 ◽  
Mdck Cells ◽  
Inhibitory Effect ◽  
Antiretroviral Drugs ◽  
Aminosalicylic Acid ◽  
P Glycoprotein ◽  
Heparg Cells ◽  
Group 5 ◽  
Almost All

ABSTRACTPredicting drug-drug interactions (DDIs) related to cytochrome P450 (CYP), such as CYP3A4 and one of the major drug transporters, P-glycoprotein (P-gp), is crucial in the development of future chemotherapeutic regimens to treat tuberculosis (TB) and TB/AIDS coinfection cases. We evaluated the effects of 30 anti-TB drugs, novel candidates, macrolides, and representative antiretroviral drugs on human CYP3A4 activity using a commercially available screening kit for CYP3A4 inhibitors and a human hepatocyte, HepaRG. Moreover, in order to estimate the interactions of these drugs with human P-gp, screening for substrates was performed. For some substrates, P-gp inhibition tests were carried out using P-gp-expressing MDCK cells. As a result, almost all the compounds showed the expected effects on human CYP3A4 both in thein vitroscreening and in HepaRG cells. Importantly, the unproven mechanisms of DDIs caused by WHO group 5 drugs, thioamides, andp-aminosalicylic acid were elucidated. Intriguingly, clofazimine (CFZ) exhibited weak inductive effects on CYP3A4 at >0.25 μM in HepaRG cells, while an inhibitory effect was observed at 1.69 μM in thein vitroscreening, suggesting that CFZ autoinduces CYP3A4 in the human liver. Our method, based on one of the pharmacokinetics parameters in humans, provides more practical information associated with not only DDIs but also with drug metabolism.

PROTECTIVE EFFECT OF POLYPEPTIDE AND AMINO ACIDS ON THE DEVELOPMENT OF THE NERVOUS TISSUE CULTURE IN THE PRESENCE OF CYCLOPHOSPHAMIDE

2017 ◽  
pp. 22-26
Author(s):  
V. B. Dolgo-Saburov ◽  
N. I. Chalisova ◽  
L. V. Lyanginen ◽  
E. S. Zalomaeva
Keyword(s):  
Amino Acids ◽  
Cell Proliferation ◽  
Tissue Culture ◽  
Protective Effect ◽  
Organotypic Culture ◽  
Inhibitory Effect ◽  
Mustard Gas ◽  
Synthesis Inhibitor ◽  
Combined Administration ◽  
The Central Nervous System

In an organotypic culture, an investigation was conducted into combined effects of cyclophosphamide DNA as synthesis inhibitor used to model a resorptive action of mustard gas, and cortexin polypeptide or each of 20 encoded amino acids on the development of cell proliferation in cerebral cortex explants of the rat. The combined administration of cyclophosphamide together with cortexin or with each of the 20 encoded amino acids, except glycine, showed suppression of the cytostatic agent inhibitory effect. Thus, cortexin and amino acids have a protective effect on cell proliferation in the tissue culture of the central nervous system under the action of mustardlike substances.

Protective influence of coded amino acids on the development of liver tissue culture in the presence of cytostatic

2020 ◽  
pp. 48-53
Author(s):  
N. I. Chalisova ◽  
V. K. Kozlov ◽  
A. B. Mulik ◽  
E. P. Zatsepin ◽  
T. A. Kostrova
Keyword(s):  
Amino Acids ◽  
Tissue Culture ◽  
Side Effects ◽  
Liver Tissue ◽  
Organotypic Culture ◽  
Growth Zone ◽  
Inhibitory Effect ◽  
Cytostatic Drugs ◽  
Urgent Problem ◽  
Combined Exposure

An urgent problem is the search for substances that can provide a protective effect in cases of DNA synthesis and repair disorders that arise as a result of side effects of cytostatic drugs used in the treatment of cancer. The aim of this work was to study the effect of 20 encoded amino acids in the presence of Cyclophosphane on the development of organotypic culture of rat liver tissue. The results obtained indicate that Cyclophosphane; which simulates the action of such cytostatic substances; inhibits cell proliferation in the liver tissue. It was also found that the encoded amino acids: asparagine; arginine; and glutamic acid; eliminate the inhibitory effect of Cyclophosphane in liver tissue culture. The growth zone of explants after combined exposure to Cyclophosphane (whose isolated action suppressed the growth zone) and these amino acids increased significantly and reached control values. Thus; the experimental data create the basis for the development of methods for the therapeutic use of the three studied amino acids for the removal of side effects in the treatment with cytostatic drugs.

Status of Flavonols as P-Glycoprotein Inhibitors in Cancer Chemotherapy

2009 ◽  
Vol 5 (2) ◽  
pp. 89-99 ◽  
Author(s):  
Tripta Bansal ◽  
Manu Jaggi ◽  
Roop Khar ◽  
Sushama Talegaonkar
Keyword(s):  
Cancer Chemotherapy ◽  
P Glycoprotein ◽  
Glycoprotein Inhibitors

Chemosensitization potential of P-glycoprotein inhibitors in malaria parasites

2013 ◽  
Vol 134 (2) ◽  
pp. 235-243 ◽  
Author(s):  
Laura M. Alcantara ◽  
Junwon Kim ◽  
Carolina B. Moraes ◽  
Caio H. Franco ◽  
Kathrin D. Franzoi ◽  
...  
Keyword(s):  
Malaria Parasites ◽  
P Glycoprotein ◽  
Glycoprotein Inhibitors

Role of cations in the flocculation of Saccharomyces cerevisiae and discrimination of the corresponding proteins

1991 ◽  
Vol 37 (5) ◽  
pp. 397-403 ◽  
Author(s):  
Hiroshi Kuriyama ◽  
Itaru Umeda ◽  
Harumi Kobayashi
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Surface ◽  
Inhibitory Effect ◽  
Surface Proteins ◽  
Promoting Effect ◽  
Yeast Strains ◽  
Yeast Flocculation ◽  
Different Types ◽  
Anionic Groups

Asexual yeast flocculation was studied using strong flocculents of Saccharomyces cerevisiae. The inhibitory effect of cations on flocculation is considered to be caused by competition between those cations and Ca2+ at the binding site of the Ca2+-requiring protein that is involved in flocculation. Inhibition of flocculation by various cations occurred in the following order: La3+, Sr2+, Ba2+, Mn2+, Al3+, and Na+. Cations such as Mg2+, Co2+, and K+ promoted flocculation. This promoting effect may be based on the reduction of electrostatic repulsive force between cells caused by binding of these cations anionic groups present on the cell surface. In flocculation induced by these cations, trace amounts of Ca2+ excreted on the cell surface may activate the corresponding protein. The ratio of Sr2+/Ca2+ below which cells flocculated varied among strains: for strains having the FLO5 gene, it was 400 to 500; for strains having the FLO1 gene, about 150; and for two alcohol yeast strains, 40 to 50. This suggests that there are several different types of cell surface proteins involved in flocculation in different yeast strains. Key words: yeast, flocculation, protein, cation, calcium.

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