Transplant drugs affect the expression of phase II and antioxidant enzymes in human carcinoma cells HepG2 but not in primary cultures of human hepatocytes: In vitro comparative study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F16%3A33159496" target="_blank" >RIV/61989592:15310/16:33159496 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S1734114016300548" target="_blank" >http://www.sciencedirect.com/science/article/pii/S1734114016300548</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.pharep.2016.06.001" target="_blank" >10.1016/j.pharep.2016.06.001</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Transplant drugs affect the expression of phase II and antioxidant enzymes in human carcinoma cells HepG2 but not in primary cultures of human hepatocytes: In vitro comparative study

Popis výsledku v původním jazyce

BACKGROUND: We carried out a test whether or not transplant drugs such as cyclosporine A, Rapamycin (Sirolimus), Tacrolimus, Everolimus and Mycophenolate mofetil affects the expression of phase II enzymes comprising of UDP-glucuronosyltransferases (UGTs) and glutathione-S-transferases (GSTs), and antioxidant enzymes that consist of glutathione reductase (GSR), glutathione peroxidase 1 (GPX1) and heme-oxygenase 1 (HMOX1). METHODS: Experiments were performed in primary cultures of human hepatocytes and in human hepatocarcinoma HepG2 cells, the models of metabolically competent and incompetent cells, respectively. We used quantitative real-time PCR. RESULTS: We found that none of the tested compounds affected the expression of investigated genes in human hepatocytes. On the other hand, Mycophenolate mofetil induced GPX1 mRNA, although it suppressed mRNA level of UGT1A4/1A9/2B7/2B10, GSTA1/O1/T1, GSR and HMOX1 in HepG2 cells. CONCLUSION: We showed that the tested transplant drugs have no effect on the expression of selected phase II and antioxidant enzymes in human hepatocytes. Nevertheless, the experiments carried out in two common and frequently used in vitro cellular models, we emphasize that finding based solely on carcinoma cells must be taken with caution when transposing to in vivo situations.

Název v anglickém jazyce

Transplant drugs affect the expression of phase II and antioxidant enzymes in human carcinoma cells HepG2 but not in primary cultures of human hepatocytes: In vitro comparative study

Popis výsledku anglicky

BACKGROUND: We carried out a test whether or not transplant drugs such as cyclosporine A, Rapamycin (Sirolimus), Tacrolimus, Everolimus and Mycophenolate mofetil affects the expression of phase II enzymes comprising of UDP-glucuronosyltransferases (UGTs) and glutathione-S-transferases (GSTs), and antioxidant enzymes that consist of glutathione reductase (GSR), glutathione peroxidase 1 (GPX1) and heme-oxygenase 1 (HMOX1). METHODS: Experiments were performed in primary cultures of human hepatocytes and in human hepatocarcinoma HepG2 cells, the models of metabolically competent and incompetent cells, respectively. We used quantitative real-time PCR. RESULTS: We found that none of the tested compounds affected the expression of investigated genes in human hepatocytes. On the other hand, Mycophenolate mofetil induced GPX1 mRNA, although it suppressed mRNA level of UGT1A4/1A9/2B7/2B10, GSTA1/O1/T1, GSR and HMOX1 in HepG2 cells. CONCLUSION: We showed that the tested transplant drugs have no effect on the expression of selected phase II and antioxidant enzymes in human hepatocytes. Nevertheless, the experiments carried out in two common and frequently used in vitro cellular models, we emphasize that finding based solely on carcinoma cells must be taken with caution when transposing to in vivo situations.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Pharmacological Reports

ISSN

1734-1140

e-ISSN

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Svazek periodika

68

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

PL - Polská republika

Počet stran výsledku

7

Strana od-do

"1008-1014"

Kód UT WoS článku

000384517600022

EID výsledku v databázi Scopus

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