Modulation of the xenobiotic transformation system and inflammatory response by ochratoxin A exposure using a co-culture system of Caco-2 and HepG2 cells

التفاصيل البيبلوغرافية
العنوان: Modulation of the xenobiotic transformation system and inflammatory response by ochratoxin A exposure using a co-culture system of Caco-2 and HepG2 cells
المؤلفون: A. Crespo-Sempere, Sonia Marín, Vicente Sanchis, Antonio J. Ramos, Cyndia Azucena González-Arias
المصدر: Repositorio Abierto de la UdL
Universitad de Lleida
Recercat. Dipósit de la Recerca de Catalunya
instname
بيانات النشر: Elsevier, 2015.
سنة النشر: 2015
مصطلحات موضوعية: Cell Survival, Cellular differentiation, Cell, Biology, Toxicology, Gene Expression Regulation, Enzymologic, Cell membrane, Cell-mediated cytotoxicity, Cytochrome P-450 Enzyme System, Gene expression, medicine, Humans, Microbiologia dels aliments, Secretion, Cytotoxicity, Micotoxines, Biotransformation, Tumors, Inflammation, Multidrug resistance-associated protein 2, Cell Membrane, General Medicine, Hep G2 Cells, Mycotoxins, Food microbiology, Molecular biology, Ochratoxins, Coculture Techniques, Citotoxicitat per mediació cel·lular, medicine.anatomical_structure, Caco-2, Caco-2 Cells, Food Science
الوصف: Cytotoxicity of ochratoxin A (OTA) was evaluated using the MTS assay, and membrane integrity was measured using transepithelial electrical resistance (TEER). A transwell system was used to investigate the effect of OTA on the expression of the CYP450 (1A1, 2A6, 2B6, 3A4 and 3A5), NAT2, COX-2, LOX-5, and MRP2 genes in Caco-2 and HepG2 cells. TEER decreased by a mean of 63.2% after 24 h in Caco-2 differentiated cells without inducing cell detachment; revealing damage to the intestinal epithelial cell tight junction proteins and an increase in cell permeability. Gene expression analysis showed that modulation of gene expression by OTA was higher in Caco-2 cells than in HepG2 cells, and generally, the duration of exposure to OTA had a more significant effect than the OTA dose. A general OTA down-regulation effect was observed in Caco-2 cells, in contrast with the down- and up-regulation observed in HepG2 cells. In Caco-2 cells, CYP1A1 was the gene with the highest regulation, followed by CYP3A4 and CYP3A5. Conversely, in HepG2 cells, CYP2B6 was highly regulated at 3 and 12 h compared to the other cytochromes; CYP1A1 was slightly modulated during the first 12 h, but an overexpression was observed at 24 h. Our data support the involvement of the COX-2 and 5-LOX genes in liver metabolism of OTA. On the basis of the gene expression analysis, the results suggest a possible impairment in OTA secretion at the intestinal and hepatic level due to MRP2 repression. In addition, we provide evidence of the effect of OTA on NAT2 gene expression, which had not been reported before. The authors are grateful to the Spanish Government (ProjectsAGL2011-24862 and AGL2014-52648-REDT) and Catalonian Government (XaRTA-Reference Network on Food Technology) for their financial support. C.A. Gonzalez-Arias thanks the Secretaria de Universitats i Recerca del Departament de Economia i Coneixementof the Generalitat de Catalunya for the pre-doctoral grant.
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8bda64a81436e050a298e56223adafecTest
https://doi.org/10.1016/j.fct.2015.10.007Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....8bda64a81436e050a298e56223adafec
قاعدة البيانات: OpenAIRE